open: No conditions. Results ordered Creators, Title.
2024-03-28T10:49:52Z
EPrints
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http://crdd.osdd.net/open/
2019-07-27T09:46:13Z
2019-07-27T11:50:17Z
http://crdd.osdd.net/open/id/eprint/2302
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2302
2019-07-27T09:46:13Z
Sequence-Structure-Function Relationship among the Ferredoxin-Like Fold proteins
Giriraj Acharya
2016-09-30T05:33:53Z
2016-09-30T05:33:53Z
http://crdd.osdd.net/open/id/eprint/1850
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1850
2016-09-30T05:33:53Z
Evolutionary relationships between heme-binding ferredoxin α + β barrels.
The α + β barrel superfamily of the ferredoxin-like fold consists of a functionally diverse group of evolutionarily related proteins. The barrel architecture of these proteins is formed by either homo-/hetero-dimerization or duplication and fusion of ferredoxin-like domains. Several members of this superfamily bind heme in order to carry out their functions.
Giriraj Acharya
Gurmeet Kaur
Srikrishna Subramanian
2017-05-19T06:07:47Z
2017-05-19T06:07:47Z
http://crdd.osdd.net/open/id/eprint/1927
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1927
2017-05-19T06:07:47Z
An atypical segment swap in the DN and DC domains of the Acr_tran family resistance-nodulation-cell division pump
Domain/segment swapping is an exchange of equivalent secondary structure element(s) among two or more protein domains resulting in the reconstitution of the original fold while simultaneously causing oligomerization. Here we report an example of the outer membrane factor docking region of the Acr_tran family (PF00873) resistance-nodulation-cell division pump, in which a swapped, misfolded state, of the ferredoxin-like fold of the DN and DC domains, effectuates oligomerization. The atypical segment swap and the associated displacement of a region of the ferredoxin-like fold leads to a topology that is distinct from the original fold. To our knowledge, such segment swaps and associated fold change are rare. This exemplifies the role of functional constraints including oligomerization that determine the interplay between sequence and the three-dimensional structure of proteins.
Giriraj Acharya
Gurmeet Kaur
Srikrishna Subramanian
2016-01-29T06:52:01Z
2016-09-30T05:34:57Z
http://crdd.osdd.net/open/id/eprint/1739
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1739
2016-01-29T06:52:01Z
CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides.
CPPsite 2.0 (http://crdd.osdd.net/raghava/cppsite/) is an updated version of manually curated database (CPPsite) of cell-penetrating peptides (CPPs). The current version holds around 1850 peptide entries, which is nearly two times than the entries in the previous version. The updated data were curated from research papers and patents published in last three years. It was observed that most of the CPPs discovered/ tested, in last three years, have diverse chemical modifications (e.g. non-natural residues, linkers, lipid moieties, etc.). We have compiled this information on chemical modifications systematically in the updated version of the database. In order to understand the structure-function relationship of these peptides, we predicted tertiary structure of CPPs, possessing both modified and natural residues, using state-of-the-art techniques. CPPsite 2.0 also maintains information about model systems (in vitro/in vivo) used for CPP evaluation and different type of cargoes (e.g. nucleic acid, protein, nanoparticles, etc.) delivered by these peptides. In order to assist a wide range of users, we developed a user-friendly responsive website, with various tools, suitable for smartphone, tablet and desktop users. In conclusion, CPPsite 2.0 provides significant improvements over the previous version in terms of data content.
Piyush Agrawal
Sherry Bhalla
Salman Sadullah Usmani
Sandeep Singh
Kumardeep Chaudhary
G.P.S. Raghava
Ankur Gautam
2016-09-30T05:30:44Z
2016-09-30T05:30:44Z
http://crdd.osdd.net/open/id/eprint/1851
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1851
2016-09-30T05:30:44Z
Genome sequence and comparative analysis of clavicipitaceous insect-pathogenic fungus Aschersonia badia with Metarhizium spp.
Aschersonia badia [(Ab) Teleomorph: Hypocrella siamensis] is an entomopathogenic fungus that specifically infects scale insects and whiteflies. We present the whole genome sequence of Ab and its comparison with two clavicipitaceous fungi Metarhizium robertsii (MR: generalist entomopathogen) and M. acridum (MAC: acridid-specific entomopathogen) that exhibit variable host preferences. Here, through comparative analysis of pathogen-host interacting genes, carbohydrate active enzymes, secondary metabolite biosynthesis genes, and sexuality genes, we explore the proteins with possible virulence functions in clavicipitaceous fungi. Comprehensive overview of GH18 family chitinases has been provided to decipher the role of chitinases in claviceptaceous fungi that are either host specific or generalists.
Yamini Agrawal
Tarun Narwani
Srikrishna Subramanian
2016-09-30T05:27:41Z
2016-09-30T05:27:41Z
http://crdd.osdd.net/open/id/eprint/1852
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1852
2016-09-30T05:27:41Z
EspR-dependent ESAT-6 Protein Secretion of Mycobacterium tuberculosis Requires the Presence of Virulence Regulator PhoP.
Attenuation of Mycobacterium bovis BCG strain is related to the loss of the RD1-encoded ESX-1 secretion system. The ESX-1 system secretes virulence factor ESAT-6 that plays a critical role in modulation of the host immune system, which is essential for establishment of a productive infection. Previous studies suggest that among the reasons for attenuation of Mycobacterium tuberculosis H37Ra is a mutation in the phoP gene that interferes with the ESX-1 secretion system and inhibits secretion of ESAT-6. Here, we identify a totally different and distinct regulatory mechanism involving PhoP and transcription regulator EspR on transcriptional control of the espACD operon, which is required for ESX-1-dependent ESAT-6 secretion. Although both of these regulators are capable of influencing espACD expression, we show that activation of espACD requires direct recruitment of both PhoP and EspR at the espACD promoter. The most fundamental insights are derived from the inhibition of EspR binding at the espACD regulatory region of the phoP mutant strain because of PhoP-EspR protein-protein interactions. Based on these results, a model is proposed suggesting how PhoP and EspR protein-protein interactions contribute to activation of espACD expression and, in turn, control ESAT-6 secretion, an essential pathogenic determinant of M. tuberculosis Together, these results have significant implications on the mechanism of virulence regulation of M. tuberculosis.
Vijjamarri Anil Kumar
Rajni Goyal
Roohi Bansal
Nisha Singh
Ritesh Rajesh Sevalkar
Ashwani Kumar
Dibyendu Sarkar
2016-09-30T05:24:05Z
2016-09-30T05:24:05Z
http://crdd.osdd.net/open/id/eprint/1853
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1853
2016-09-30T05:24:05Z
Structural Analysis of the Myo1c and Neph1 Complex Provides Insight into the Intracellular Movement of Neph1.
The Myo1c motor functions as a cargo transporter supporting various cellular events, including vesicular trafficking, cell migration, and stereociliary movements of hair cells. Although its partial crystal structures were recently described, the structural details of its interaction with cargo proteins remain unknown. This study presents the first structural demonstration of a cargo protein, Neph1, attached to Myo1c, providing novel insights into the role of Myo1c in intracellular movements of this critical slit diaphragm protein. Using small angle X-ray scattering studies, models of predominant solution conformation of unliganded full-length Myo1c and Myo1c bound to Neph1 were constructed. The resulting structures show an extended S-shaped Myo1c with Neph1 attached to its C-terminal tail. Importantly, binding of Neph1 did not induce a significant shape change in Myo1c, indicating this as a spontaneous process or event. Analysis of interaction surfaces led to the identification of a critical residue in Neph1 involved in binding to Myo1c. Indeed, a point mutant from this site abolished interaction between Neph1 and Myo1c when tested in the in vitro and in live-cell binding assays. Live-cell imaging, including fluorescence recovery after photobleaching, provided further support for the role of Myo1c in intracellular vesicular movement of Neph1 and its turnover at the membrane.
Ehtesham Arif
Pankaj Sharma
Ashish Solanki
Leena Mallik
Yogendra S Rathore
Waleed O Twal
Samir K Nath
Darpan Gandhi
Lawrence B Holzman
E Michael Ostap
. Ashish
Deepak Nihalani
2016-02-17T10:49:07Z
2016-09-30T05:24:59Z
http://crdd.osdd.net/open/id/eprint/1831
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1831
2016-02-17T10:49:07Z
Biosurfactant as a Promoter of Methane Hydrate Formation: Thermodynamic and Kinetic Studies.
Natural gas hydrates (NGHs) are solid non-stoichiometric compounds often regarded as a next generation energy source. Successful commercialization of NGH is curtailed by lack of efficient and safe technology for generation, dissociation, storage and transportation. The present work studied the influence of environment compatible biosurfactant on gas hydrate formation. Biosurfactant was produced by Pseudomonas aeruginosa strain A11 and was characterized as rhamnolipids. Purified rhamnolipids reduced the surface tension of water from 72 mN/m to 36 mN/m with Critical Micelle Concentration (CMC) of 70 mg/l. Use of 1000 ppm rhamnolipids solution in C type silica gel bed system increased methane hydrate formation rate by 42.97% and reduced the induction time of hydrate formation by 22.63% as compared to water saturated C type silica gel. Presence of rhamnolipids also shifted methane hydrate formation temperature to higher values relative to the system without biosurfactant. Results from thermodynamic and kinetic studies suggest that rhamnolipids can be applied as environment friendly methane hydrate promoter.
Amit Arora
Swaranjit Singh Cameotra
Rajnish Kumar
Chandrajit Balomajumder
Anil Kumar Singh
B Santhakumari
Pushpendra Kumar
Sukumar Laik
2019-08-03T09:28:38Z
2019-08-03T11:45:34Z
http://crdd.osdd.net/open/id/eprint/2318
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2318
2019-08-03T09:28:38Z
Understanding effects of temperature on Shape-function Relationship of Gelsolin and its F-Actin Depolymerising Competent Versions
Maulik D Badmalia
2019-07-27T09:22:27Z
2019-07-27T11:44:43Z
http://crdd.osdd.net/open/id/eprint/2298
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2298
2019-07-27T09:22:27Z
Molecular and genetic characterization of antimicrobial peptides produced by soil bacterial isolates
Piyush Baindara
2016-09-30T05:19:32Z
2016-09-30T05:19:32Z
http://crdd.osdd.net/open/id/eprint/1854
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1854
2016-09-30T05:19:32Z
Isolation and characterization of a novel Gram-negative bacterium Chromobacterium alkanivorans sp. nov., strain IITR-71T degrading halogenated alkanes.
The taxonomic position of a Gram-stain-negative, non-violacein pigmented bacterium isolated from an insecticide contaminated site was characterized by a polyphasic approach. The bacterium was able to grow on three different halogenated compounds namely 1-Chlorobutane, 1-Chloropropane and 1, 2-Dichlorethane. As a critical step in the degradation of these haloalkanes, stoichiometric amounts of dechlorination were estimated. Based on selective enrichment method for three months, using a highly contaminated mixed chemical soil, a bacterium was obtained and designated as IITR-71T. Its versatility and novelty led us to further characterize by polyphasic taxonomy. The 16S rRNA gene sequence (1446 bases) comparison showed highest similarity with those of genus Chromobacterium with the closely related species to strain IITR-71T are Chromobacterium aquaticum (99.3%) followed by Chromobacterium haemolyticum (98.6%) and Chromobacterium piscinae (97.1%). The major ubiquinone was Q-8. Predominant polar lipids are phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG). The DNA G+C content of strain IITR-71T was estimated to be 61.2 mol%. The results of genotypic and phenotypic distinctiveness of the strain IITR-71T with its phylogenetic relationship suggests that the strain IITR-71T is a novel species, for which the name Chromobacterium alkanivorans sp. nov. is proposed. The type strain is IITR-71T (= MTCC 11059T = JCM 30068T = KCTC 52433T).
Abhay Bajaj
Anand Kumar
Shivani Yadav
Gurwinder Kaur
Monu Bala
Nitin Kumar Singh
Rajendran Mathan Kumar
Natesan Manickam
Shanmugam Mayilraj
2019-07-27T09:55:18Z
2019-07-27T11:53:13Z
http://crdd.osdd.net/open/id/eprint/2304
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2304
2019-07-27T09:55:18Z
Investigating the Role of Adopted Orphan Nuclear Receptor in Infection,Inflammation and Cancer
Ella Bhagyaraj
2016-09-30T05:16:36Z
2016-09-30T05:16:36Z
http://crdd.osdd.net/open/id/eprint/1855
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1855
2016-09-30T05:16:36Z
Human Xenobiotic Nuclear Receptor PXR Augments Mycobacterium tuberculosis Survival.
Mycobacterium tuberculosis can evade host defense processes, thereby ensuring its survival and pathogenesis. In this study, we investigated the role of nuclear receptor, pregnane X receptor (PXR), in M. tuberculosis infection in human monocyte-derived macrophages. In this study, we demonstrate that PXR augments M. tuberculosis survival inside the host macrophages by promoting the foamy macrophage formation and abrogating phagolysosomal fusion, inflammation, and apoptosis. Additionally, M. tuberculosis cell wall lipids, particularly mycolic acids, crosstalk with human PXR (hPXR) by interacting with its promiscuous ligand binding domain. To confirm our in vitro findings and to avoid the reported species barrier in PXR function, we adopted an in vivo mouse model expressing hPXR, wherein expression of hPXR in mice promotes M. tuberculosis survival. Therefore, pharmacological intervention and designing antagonists to hPXR may prove to be a promising adjunct therapy for tuberculosis.
Ella Bhagyaraj
Ravikanth Nanduri
Ankita Saini
Hedwin Kitdorlang Dkhar
Nancy Ahuja
Vemika Chandra
Sahil Mahajan
Rashi Kalra
Drishti Tiwari
Charu Sharma
Ashok Kumar Janmeja
Pawan Gupta
2019-07-27T10:44:31Z
2020-01-04T12:08:25Z
http://crdd.osdd.net/open/id/eprint/2315
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2315
2019-07-27T10:44:31Z
Studies on gcp-alr gene cluster of Mycobacterium tuberculosis and development of in silico analysis tools along with a database for prokaryotic glycoproteins
Aadil Hussain Bhat
2019-07-27T10:21:14Z
2019-07-29T09:03:51Z
http://crdd.osdd.net/open/id/eprint/2310
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2310
2019-07-27T10:21:14Z
Understanding the Redox biology of tuberculosis pathogenesis using genetically encoded sensors
Ahmad Shabir Bhat
2018-03-26T10:42:02Z
2018-04-03T07:09:13Z
http://crdd.osdd.net/open/id/eprint/1943
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1943
2018-03-26T10:42:02Z
Imaging the NADH:NAD+ Homeostasis for Understanding the Metabolic Response of Mycobacterium to Physiologically Relevant Stresses
The NADH:NAD+ ratio is the primary indicator of the metabolic state of bacteria. NAD(H) homeostasis is critical for Mycobacterium tuberculosis (Mtb) survival and is thus considered an important drug target, but the spatio-temporal measurements of NAD(H) remain a challenge. Genetically encoded fluorescent biosensors of the NADH:NAD+ ratios were recently described, paving the way for investigations of the metabolic state of pathogens during infection. Here we have adapted the genetically encoded biosensor Peredox for measurement of the metabolic state of Mtb in vitro and during infection of macrophage cells. Using Peredox, here we show that inhibition of the electron transport chain, disruption of the membrane potential and proton gradient, exposure to reactive oxygen species and treatment with antimycobacterial drugs led to the accumulation of NADH in mycobacterial cells. We have further demonstrated that Mtb residing in macrophages displays higher NADH:NAD+ ratios, that may indicate a metabolic stress faced by the intracellular Mtb. We also demonstrate that the Mtb residing in macrophages display a metabolic heterogeneity, which may perhaps explain the tolerance displayed by intracellular Mtb. Next we studied the effect of immunological modulation by interferon gamma on metabolism of intracellular Mtb, since macrophage activation is known to restrict mycobacterial growth. We observed that activation of resting macrophages with interferon-gamma results in higher NADH:NAD+ levels in resident Mtb cells. We have further demonstrated that exposure of Isoniazid, Bedaquiline, Rifampicin, and O-floxacin results in higher NADH:NAD+ ratios in the Mtb residing in macrophages. However, intracellular Mtb displays lower NADH:NAD+ ratio upon exposure to clofazimine. In summary, we have generated reporter strains capable of measuring the metabolic state of Mtb cells in vitro and in vivo with spatio-temporal resolution. We believe that this tool will facilitate further studies on mycobacterial physiology and will create new avenues of research for anti-tuberculosis drug discovery.
SA Bhatt
Iram K. Iqbal
Ashwani Kumar
2019-08-03T09:51:22Z
2019-08-03T11:50:36Z
http://crdd.osdd.net/open/id/eprint/2324
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2324
2019-08-03T09:51:22Z
Construction of genetic tools for Candida species
Swati Bijlani
2019-07-27T09:51:03Z
2019-07-27T11:51:40Z
http://crdd.osdd.net/open/id/eprint/2303
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2303
2019-07-27T09:51:03Z
Exploring the potential of F-Type lectins to direct biological functions
Ritika Bishnoi
2016-09-30T05:14:13Z
2016-09-30T05:14:13Z
http://crdd.osdd.net/open/id/eprint/1856
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1856
2016-09-30T05:14:13Z
Mycobacterium tuberculosis H37Ra: a surrogate for the expression of conserved, multimeric proteins of M.tb H37Rv.
Obtaining sufficient quantities of recombinant M.tb proteins using traditional approaches is often unsuccessful. Several enzymes of the glycolytic cycle are known to be multifunctional, however relatively few enzymes from M.tb H37Rv have been characterized in the context of their enzymatic and pleiotropic roles. One of the primary reasons is the difficulty in obtaining sufficient amounts of functionally active protein.
Vishant Mahendra Boradia
Pravinkumar Patil
Anushri Agnihotri
Ajay Kumar
Kalpesh Kumar Rajwadi
Ankit Sahu
Naveen Bhagath
Navdeep Sheokand
Manoj Kumar
Himanshu Malhotra
Rachita Patkar
Navi Hasan
Manoj Raje
Chaaya Iyengar Raje
2016-09-30T05:11:52Z
2016-09-30T05:11:52Z
http://crdd.osdd.net/open/id/eprint/1857
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1857
2016-09-30T05:11:52Z
Genome Sequencing of Serinicoccus chungangensis Strain CD08_5 Isolated from Duodenal Mucosa of a Celiac Disease Patient.
For the first time, we report here the 3.5-Mb genome of Serinicoccus chungangensis strain CD08_5, isolated from duodenal mucosa from a celiac disease (CD) patient. The specific annotations obtained revealed genes associated with virulence, disease, and defense, which predict its probable role in the pathogenesis of CD.
Atul Munish Chander
Gurwinder Kaur
Ramesan Girish Nair
Devinder Kumar Dhawan
Rakesh Kochhar
Shanmugam Mayilraj
Sanjay Kumar Bhadada
2016-09-30T05:09:53Z
2016-09-30T05:09:53Z
http://crdd.osdd.net/open/id/eprint/1858
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1858
2016-09-30T05:09:53Z
Genome Sequence of Kocuria palustris Strain CD07_3 Isolated from the Duodenal Mucosa of a Celiac Disease Patient.
We report here the 2.8-Mb genome of Kocuria palustris strain CD07_3 isolated from the duodenal mucosa of a celiac disease (CD) patient. The genome of the bacterium consists of specific virulence factor genes and antibiotic resistance genes that depict its pathogenic potential.
Atul Munish Chander
Ramesan Girish Nair
Gurwinder Kaur
Rakesh Kochhar
Shanmugam Mayilraj
Devinder Kumar Dhawan
Sanjay Kumar Bhadada
2016-09-30T04:56:11Z
2016-09-30T04:56:11Z
http://crdd.osdd.net/open/id/eprint/1859
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1859
2016-09-30T04:56:11Z
Transcription factors and cognate signalling cascades in the regulation of autophagy.
Autophagy is a process that maintains the equilibrium between biosynthesis and the recycling of cellular constituents; it is critical for avoiding the pathophysiology that results from imbalance in cellular homeostasis. Recent reports indicate the need for the design of high-throughput screening assays to identify targets and small molecules for autophagy modulation. For such screening, however, a better understanding of the regulation of autophagy is essential. In addition to regulation by various signalling cascades, regulation of gene expression by transcription factors is also critical. This review focuses on the various transcription factors as well as the corresponding signalling molecules that act together to translate the stimuli to effector molecules that up- or downregulate autophagy. This review rationalizes the importance of these transcription factors functioning in tandem with cognate signalling molecules and their interfaces as possible therapeutic targets for more specific pharmacological interventions.
Vemika Chandra
Ella Bhagyaraj
Raman Parkesh
Pawan Gupta
2016-09-30T04:54:08Z
2016-09-30T04:54:08Z
http://crdd.osdd.net/open/id/eprint/1860
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1860
2016-09-30T04:54:08Z
A Web Server and Mobile App for Computing Hemolytic Potency of Peptides.
Numerous therapeutic peptides do not enter the clinical trials just because of their high hemolytic activity. Recently, we developed a database, Hemolytik, for maintaining experimentally validated hemolytic and non-hemolytic peptides. The present study describes a web server and mobile app developed for predicting, and screening of peptides having hemolytic potency. Firstly, we generated a dataset HemoPI-1 that contains 552 hemolytic peptides extracted from Hemolytik database and 552 random non-hemolytic peptides (from Swiss-Prot). The sequence analysis of these peptides revealed that certain residues (e.g., L, K, F, W) and motifs (e.g., "FKK", "LKL", "KKLL", "KWK", "VLK", "CYCR", "CRR", "RFC", "RRR", "LKKL") are more abundant in hemolytic peptides. Therefore, we developed models for discriminating hemolytic and non-hemolytic peptides using various machine learning techniques and achieved more than 95% accuracy. We also developed models for discriminating peptides having high and low hemolytic potential on different datasets called HemoPI-2 and HemoPI-3. In order to serve the scientific community, we developed a web server, mobile app and JAVA-based standalone software (http://crdd.osdd.net/raghava/hemopi/).
Kumardeep Chaudhary
Ritesh Kumar
Sandeep Singh
Abhishek Tuknait
Ankur Gautam
Deepika Mathur
Priya Anand
Grish C Varshney
G.P.S. Raghava
2016-09-29T11:06:26Z
2016-09-29T11:06:26Z
http://crdd.osdd.net/open/id/eprint/1832
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1832
2016-09-29T11:06:26Z
Prediction of Immunomodulatory potential of an RNA sequence for designing non-toxic siRNAs and RNA-based vaccine adjuvants.
Our innate immune system recognizes a foreign RNA sequence of a pathogen and activates the immune system to eliminate the pathogen from our body. This immunomodulatory potential of RNA can be used to design RNA-based immunotherapy and vaccine adjuvants. In case of siRNA-based therapy, the immunomodulatory effect of an RNA sequence is unwanted as it may cause immunotoxicity. Thus, we developed a method for designing a single-stranded RNA (ssRNA) sequence with desired immunomodulatory potentials, for designing RNA-based therapeutics, immunotherapy and vaccine adjuvants. The dataset used for training and testing our models consists of 602 experimentally verified immunomodulatory oligoribonucleotides (IMORNs) that are ssRNA sequences of length 17 to 27 nucleotides and 520 circulating miRNAs as non-immunomodulatory sequences. We developed prediction models using various features that include composition-based features, binary profile, selected features, and hybrid features. All models were evaluated using five-fold cross-validation and external validation techniques; achieving a maximum mean Matthews Correlation Coefficient (MCC) of 0.86 with 93% accuracy. We identified motifs using MERCI software and observed the abundance of adenine (A) in motifs. Based on the above study, we developed a web server, imRNA, comprising of various modules important for designing RNA-based therapeutics (http://crdd.osdd.net/raghava/imrna/).
Kumardeep Chaudhary
Gandharva Nagpal
Sandeep Kumar Dhanda
G.P.S. Raghava
2016-09-29T11:01:39Z
2016-09-29T11:01:39Z
http://crdd.osdd.net/open/id/eprint/1839
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1839
2016-09-29T11:01:39Z
Methylobacterium indicum sp. nov., a facultative methylotrophic bacterium isolated from rice seed.
Two pink pigmented, Gram-negative, motile, aerobic, rod shaped endophytic bacteria designated as SE2.11(T) and SE3.6 were isolated in different experiments from surface sterilized rice seeds. Both strains grew optimally at 28°C temperature. They were positive for catalase and nitrate reduction. The 16S rRNA gene sequence of the strains SE2.11(T) and SE3.6 displayed between 98.1% and 97.2% similarities with the validly published species of the genus Methylobacterium. The major cellular fatty acid was C18:1 ω7c in both the strains, a characteristic feature observed for members of the genus Methylobacterium. The predominant polar lipids were phospholipids including phosphatidylglycerol (PG), phosphatidylethanolamine (PE) and diphosphatidylglycerol (DPG). Phylogenetic analysis of 16S rRNA gene sequences resulted in the formation of a coherent cluster of strains SE2.11(T) and SE3.6 with closest relative Methylobacterium platani JCM 14648(T). However, digital DNA-DNA hybridization (dDDH) of strains SE2.11(T) and SE3.6 with the closest type strain M. platani JCM 14648(T) revealed similarity of 35.5% and 35.4%, respectively. Further, the ANI analysis of strains SE2.11(T) and SE3.6 genomes revealed only 87.9% identity with M. platani JCM 14648(T). Based on differences in biochemical, chemotaxonomic characteristics along with low identity at whole genome level we conclude that both strains represent a novel species of the genus Methylobacterium, for which the name Methylobacterium indicum sp. nov., is proposed. The type strain Methylobacterium indicum is SE2.11(T) (=MTCC 12298(T)=JCM 30761(T)) and SE3.6 (=MTCC 12299=JCM 30762) is another strain.
Vasvi Chaudhry
Piyush Baindara
Vijay Kumar Pal
Niharika Chawla
Prabhu B Patil
Suresh Korpole
2016-09-29T11:03:48Z
2016-09-29T11:03:48Z
http://crdd.osdd.net/open/id/eprint/1840
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1840
2016-09-29T11:03:48Z
Genomic investigation reveals evolution and lifestyle adaptation of endophytic Staphylococcus epidermidis.
Staphylococcus epidermidis is a major human associated bacterium and also an emerging nosocomial pathogen. There are reports of its association to rodents, sheep and plants. However, comparative and evolutionary studies of ecologically diverse strains of S. epidermidis are lacking. Here, we report the whole genome sequences of four S. epidermidis strains isolated from surface sterilized rice seeds along with genome sequence of type strain. Phylogenomic analysis of rice endophytic S. epidermidis (RESE) with "type strain" unequivocally established their species identity. Whole genome based tree of 93 strains of S. epidermidis revealed RESE as distinct sub-lineage which is more related to rodent sub-lineage than to majority of human lineage strains. Furthermore, comparative genomics revealed 20% variable gene-pool in S. epidermidis, suggesting that genomes of ecologically diverse strains are under flux. Interestingly, we were also able to map several genomic regions that are under flux and gave rise to RESE strains. The largest of these genomic regions encodes a cluster of genes unique to RESE that are known to be required for survival and stress tolerance, apart from those required for adaptation to plant habitat. The genomes and genes of RESE represent distinct ecological resource/sequences and provided first evolutionary insights into adaptation of S. epidermidis to plants.
Vasvi Chaudhry
Prabhu B Patil
2019-07-20T10:45:10Z
2019-07-20T11:43:06Z
http://crdd.osdd.net/open/id/eprint/2295
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2295
2019-07-20T10:45:10Z
Characterization of mammalian cell surface GAPDH as novel plasminogen receptor and its mechanism of membrane trafficking
Anoop Singh Chauhan
2019-07-27T09:28:24Z
2019-07-27T11:45:47Z
http://crdd.osdd.net/open/id/eprint/2299
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2299
2019-07-27T09:28:24Z
Molecular analysis of the OmpR/EnvZ signaling system in conferring antimicrobial resistance in Acinetobacter baumannii
Neeraj Kumar Chauhan
2016-09-29T10:59:38Z
2016-09-29T10:59:38Z
http://crdd.osdd.net/open/id/eprint/1861
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1861
2016-09-29T10:59:38Z
SMEpred workbench: a web server for predicting efficacy of chemically modified siRNAs.
Chemical modifications have been extensively exploited to circumvent shortcomings in therapeutic applications of small interfering RNAs (siRNAs). However, experimental designing and testing of these siRNAs or chemically modified siRNAs (cm-siRNAs) involves enormous resources. Therefore, in-silico intervention in designing cm-siRNAs would be of utmost importance. We developed SMEpred workbench to predict the efficacy of normal siRNAs as well as cm-siRNAs using 3031 heterogeneous cm-siRNA sequences from siRNAmod database. These include 30 frequently used chemical modifications on different positions of either siRNA strand. Support Vector Machine (SVM) was employed to develop predictive models utilizing various sequence features namely mono-, di-nucleotide composition, binary pattern and their hybrids. We achieved highest Pearson Correlation Coefficient (PCC) of 0.80 during 10-fold cross validation and similar PCC value in independent validation. We have provided the algorithm in the 'SMEpred' pipeline to predict the normal siRNAs from the gene or mRNA sequence. For multiple modifications, we have assembled 'MultiModGen' module to design multiple modifications and further process them to evaluate their predicted efficacies. SMEpred webserver will be useful to scientific community engaged in use of RNAi-based technology as well as for therapeutic development. Web server is available for public use at following URL address: http://bioinfo.imtech.res.in/manojk/smepred .
Showkat Ahmad Dar
Amit Kumar Gupta
Anamika Thakur
Manoj Kumar
2016-10-04T06:18:16Z
2016-10-04T06:18:16Z
http://crdd.osdd.net/open/id/eprint/1919
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1919
2016-10-04T06:18:16Z
siRNAmod: A database of experimentally validated chemically modified siRNAs.
Small interfering RNA (siRNA) technology has vast potential for functional genomics and development of therapeutics. However, it faces many obstacles predominantly instability of siRNAs due to nuclease digestion and subsequently biologically short half-life. Chemical modifications in siRNAs provide means to overcome these shortcomings and improve their stability and potency. Despite enormous utility bioinformatics resource of these chemically modified siRNAs (cm-siRNAs) is lacking. Therefore, we have developed siRNAmod, a specialized databank for chemically modified siRNAs. Currently, our repository contains a total of 4894 chemically modified-siRNA sequences, comprising 128 unique chemical modifications on different positions with various permutations and combinations. It incorporates important information on siRNA sequence, chemical modification, their number and respective position, structure, simplified molecular input line entry system canonical (SMILES), efficacy of modified siRNA, target gene, cell line, experimental methods, reference etc. It is developed and hosted using Linux Apache MySQL PHP (LAMP) software bundle. Standard user-friendly browse, search facility and analysis tools are also integrated. It would assist in understanding the effect of chemical modifications and further development of stable and efficacious siRNAs for research as well as therapeutics. siRNAmod is freely available at: http://crdd.osdd.net/servers/sirnamod.
Showkat Ahmad Dar
Anamika Thakur
Abid Qureshi
Manoj Kumar
2019-07-20T10:16:58Z
2019-07-20T11:47:15Z
http://crdd.osdd.net/open/id/eprint/2291
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2291
2019-07-20T10:16:58Z
Identification of component(s)from Mycobacterium tuberculosis and infected macrophages having potential as biomarker(s)in Tuberculosis
Lahari Das
2019-08-03T09:23:29Z
2019-08-03T11:44:35Z
http://crdd.osdd.net/open/id/eprint/2317
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2317
2019-08-03T09:23:29Z
Molecular and Proteomic studies on Truncated Haemoglobins of Mycobacteria
Himani Datta
2016-09-29T10:56:24Z
2016-09-29T10:56:24Z
http://crdd.osdd.net/open/id/eprint/1862
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1862
2016-09-29T10:56:24Z
A web-based resource for designing therapeutics against Ebola Virus.
In this study, we describe a web-based resource, developed for assisting the scientific community in designing an effective therapeutics against the Ebola virus. Firstly, we predicted and identified experimentally validated epitopes in each of the antigens/proteins of the five known ebolaviruses. Secondly, we generated all the possible overlapping 9mer peptides from the proteins of ebolaviruses. Thirdly, conserved peptides across all the five ebolaviruses (four human pathogenic species) with no identical sequence in the human proteome, based on 1000 Genomes project, were identified. Finally, we identified peptide or epitope-based vaccine candidates that could activate both the B- and T-cell arms of the immune system. In addition, we also identified efficacious siRNAs against the mRNA transcriptome (absent in human transcriptome) of all the five ebolaviruses. It was observed that three species can potentially be targeted by a single siRNA (19mer) and 75 siRNAs can potentially target at least two species. A web server, EbolaVCR, has been developed that incorporates all the above information and useful computational tools (http://crdd.osdd.net/oscadd/ebola/).
Sandeep Kumar Dhanda
Kumardeep Chaudhary
Sudheer Gupta
Samir Kumar Brahmachari
G.P.S. Raghava
2018-03-28T02:56:54Z
2018-03-28T02:56:54Z
http://crdd.osdd.net/open/id/eprint/2032
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2032
2018-03-28T02:56:54Z
Novelin silicotools for designing peptide-based subunit vaccines and immunotherapeutics
The conventional approach for designing vaccine against a particular disease involves stimulation of the immune system using the whole pathogen responsible for the disease. In the post-genomic era, a major challenge is to identify antigenic regions or epitopes that can stimulate different arms of the immune system. In the past two decades, numerous methods and databases have been developed for designing vaccine or immunotherapy against various pathogen-causing diseases. This review describes various computational resources important for designing subunit vaccines or epitope-based immunotherapy. First, different immunological databases are described that maintain epitopes, antigens and vaccine targets. This is followed by in silico tools used for predicting linear and conformational B-cell epitopes required for activating humoral immunity. Finally, information on T-cell epitope prediction methods is provided that includes indirect methods like prediction of Major Histocompatibility Complex and transporter-associated protein binders. Different studies for validating the predicted epitopes are also examined critically. This review enlists novel in silico resources and tools available for predicting humoral and cell-mediated immune potential. These predicted epitopes could be used for designing epitope-based vaccines or immunotherapy as they may activate the adaptive immunity. Authors emphasized the need to develop tools for the prediction of adjuvants to activate innate and adaptive immune system simultaneously. In addition, attention has also been given to novel prediction methods to predict general therapeutic properties of peptides like half-life, cytotoxicity and immune toxicity.
Sandeep Kumar Dhanda
Salman Sadullah Usmani
Piyush Agrawal
Gandharva Nagpal
Ankur Gautam
G.P.S. Raghava
2016-09-29T10:54:16Z
2016-09-29T10:54:16Z
http://crdd.osdd.net/open/id/eprint/1863
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1863
2016-09-29T10:54:16Z
A Web-Based Platform for Designing Vaccines against Existing and Emerging Strains of Mycobacterium tuberculosis.
Development of an effective vaccine against drug-resistant Mycobacterium tuberculosis (Mtb) is crucial for saving millions of premature deaths every year due to tuberculosis. This paper describes a web portal developed for assisting researchers in designing vaccines against emerging Mtb strains using traditional and modern approaches. Firstly, we annotated 59 genomes of Mycobacterium species to understand similarity/dissimilarity between tuberculoid, non-tuberculoid and vaccine strains at genome level. Secondly, antigen-based vaccine candidates have been predicted in each Mtb strain. Thirdly, epitopes-based vaccine candidates were predicted/discovered in above antigen-based vaccine candidates that can stimulate all arms of immune system. Finally, a database of predicted vaccine candidates at epitopes as well at antigen level has been developed for above strains. In order to design vaccine against a newly sequenced genome of Mtb strain, server integrates three modules for identification of strain-, antigen-, epitope-specific vaccine candidates. We observed that 103,522 unique peptides (9mers) had the potential to induce an antibody response and/or promiscuous binder to MHC alleles and/or have the capability to stimulate T lymphocytes. In summary, this web-portal will be useful for researchers working on designing vaccines against Mtb including drug-resistant strains.
Sandeep Kumar Dhanda
Pooja Vir
Deepak Singla
Sudheer Gupta
Shailesh Kumar
G.P.S. Raghava
2016-09-29T10:51:35Z
2016-09-29T10:51:35Z
http://crdd.osdd.net/open/id/eprint/1864
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1864
2016-09-29T10:51:35Z
A novel secondary structure based on fused five-membered rings motif.
An analysis of protein structures indicates the existence of a novel, fused five-membered rings motif, comprising of two residues (i and i + 1), stabilized by interresidue Ni+1-H∙∙∙Ni and intraresidue Ni+1-H∙∙∙O=Ci+1 hydrogen bonds. Fused-rings geometry is the common thread running through many commonly occurring motifs, such as β-turn, β-bulge, Asx-turn, Ser/Thr-turn, Schellman motif, and points to its structural robustness. A location close to the beginning of a β-strand is rather common for the motif. Devoid of side chain, Gly seems to be a key player in this motif, occurring at i, for which the backbone torsion angles cluster at ~(-90°, -10°) and (70°, 20°). The fused-rings structures, distant from each other in sequence, can hydrogen bond with each other, and the two segments aligned to each other in a parallel fashion, give rise to a novel secondary structure, topi, which is quite common in proteins, distinct from two major secondary structures, α-helix and β-sheet. Majority of the peptide segments making topi are identified as aggregation-prone and the residues tend to be conserved among homologous proteins.
Jesmita Dhar
Raghuvansh Kishore
Pinak Chakrabarti
2019-08-03T09:18:57Z
2019-08-03T11:43:34Z
http://crdd.osdd.net/open/id/eprint/2316
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2316
2019-08-03T09:18:57Z
Understanding Gelsolin(s) Mediated Gold and Silver Nanoparticle Synthesis
Kunzes Dolma
2016-09-29T10:49:32Z
2018-10-31T06:07:47Z
http://crdd.osdd.net/open/id/eprint/1835
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1835
2016-09-29T10:49:32Z
Microbial glycolipoprotein-capped silver nanoparticles as emerging antibacterial agents against cholera.
With the increased number of cholera outbreaks and emergence of multidrug resistance in Vibrio cholerae strains it has become necessary for the scientific community to devise and develop novel therapeutic approaches against cholera. Recent studies have indicated plausibility of therapeutic application of metal nano-materials. Among these, silver nanoparticles (AgNPs) have emerged as a potential antimicrobial agent to combat infectious diseases. At present nanoparticles are mostly produced using physical or chemical techniques which are toxic and hazardous. Thus exploitation of microbial systems could be a green eco-friendly approach for the synthesis of nanoparticles having similar or even better antimicrobial activity and biocompatibility. Hence, it would be worth to explore the possibility of utilization of microbial silver nanoparticles and their conjugates as potential novel therapeutic agent against infectious diseases like cholera.
Geeta Gahlawat
Sristy Shikha
Baldev Singh Chaddha
Saumya Ray Chaudhuri
Shanmugam Mayilraj
Anirban Roy Choudhury
2016-09-29T10:47:06Z
2016-09-29T10:47:06Z
http://crdd.osdd.net/open/id/eprint/1865
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1865
2016-09-29T10:47:06Z
Interaction of Erp Protein of Mycobacterium tuberculosis with Rv2212 Enhances Intracellular Survival of Mycobacterium smegmatis.
The Mycobacterium tuberculosis exported repetitive protein (RvErp) is a crucial virulence-associated factor as determined by its role in the survival and multiplication of mycobacteria in cultured macrophages and in vivo Although attempts have been made to understand the function of Erp protein, its exact role in Mycobacterium pathogenesis is still elusive. One way to determine this is by searching for novel interactions of RvErp. Using a yeast two-hybrid assay, an adenylyl cyclase (AC), Rv2212, was found to interact with RvErp. The interaction between RvErp and Rv2212 is direct and occurs at the endogenous level. The Erp protein of Mycobacterium smegmatis (MSMEG_6405, or MsErp) interacts neither with Rv2212 nor with Ms_4279, the M. smegmatis homologue of Rv2212. Deletion mutants of Rv2212 revealed its adenylyl cyclase domain to be responsible for the interaction. RvErp enhances Rv2212-mediated cyclic AMP (cAMP) production. Also, the biological significance of the interaction between RvErp and Rv2212 was demonstrated by the enhanced survival of M. smegmatis within THP-1 macrophages. Taken together, these studies address a novel mechanism by which Erp executes its function.
Arsheed Ahmad Ganaie
Garima Trivedi
Amanpreet Kaur
Sidharth Shankar Jha
Shashi Anand
Vibhuti Rana
Amit Singh
Shekhar Kumar
Charu Sharma
2018-03-27T03:19:49Z
2018-03-27T03:19:49Z
http://crdd.osdd.net/open/id/eprint/1929
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1929
2018-03-27T03:19:49Z
Purification and characterization of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) from pea seeds
Glyceraldehyde-3-phosphate dehydrogenase [GAPDH, NAD + oxidoreductase (phosphorylating) 1.2.1.12] catalyzes the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate coupled with the reduction of NAD(+) to NADH. In addition to its role in glycolysis, this enzyme has numerous alternate functions, in both prokaryotes and eukaryotes. In plants, additional functions have been reported from multiple species including Pisum sativum. A recent study has identified that GAPDH may play an important role in seed ageing and programmed cell death. Despite this the existing purification protocols are almost 40 years old, and only partial characterization of the enzyme has been reported. In the current study, we report a modified method for purification of enzymatically active pea seed GAPDH along with the characterization of the enzyme. Using 2D gel electrophoresis our study also demonstrates that pea seeds contain four isoforms of NAD(+) dependent GAPDH.
Zahid Gani
Vishant Mahendra Boradia
Janaki Raghu Ram
Prashant Mohan Suryavanshi
Pravinkumar Patil
Santosh Kumar
Ranvir Singh
Manoj Raje
Chaaya Iyengar Raje
2019-08-03T10:08:28Z
2019-08-03T11:54:05Z
http://crdd.osdd.net/open/id/eprint/2327
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2327
2019-08-03T10:08:28Z
Metagenomic approach to explore enzymes with cellulose degrading activity
Roma Garg
2018-03-26T10:24:31Z
2018-03-26T10:24:31Z
http://crdd.osdd.net/open/id/eprint/1955
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1955
2018-03-26T10:24:31Z
Biochemical and structural characterization of a novel halotolerant cellulase from soil metagenome
ellulase catalyzes the hydrolysis of β-1,4-linkages of cellulose to produce industrially relevant monomeric subunits. Cellulases find their applications in pulp and paper, laundry, food and feed, textile, brewing industry and in biofuel production. These industries always have great demand for cellulases that can work efficiently even in harsh conditions such as high salt, heat, and acidic environments. While, cellulases with high thermal and acidic stability are already in use, existence of a high halotolerant cellulase is still elusive. Here, we report a novel cellulase Cel5R, obtained from soil metagenome that shows high halotolerance and thermal stability. The biochemical and functional characterization of Cel5R revealed its endoglucanase activity and high halostability. In addition, the crystal structure of Cel5R determined at 2.2 Å resolution reveals a large number of acidic residues on the surface of the protein that contribute to the halophilic nature of this enzyme. Moreover, we demonstrate that the four free and non-conserved cysteine residues (C65, C90, C231 and C273) contributes to the thermal stability of Cel5R by alanine scanning experiments. Thus, the newly identified endoglucanase Cel5R is a promising candidate for various industrial applications.
Roma Garg
Ritika Srivastava
Vijaya Brahma
Lata Verma
Subramanian Karthikeyan
Girish Sahni
2016-09-29T10:42:41Z
2016-09-29T10:42:41Z
http://crdd.osdd.net/open/id/eprint/1867
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1867
2016-09-29T10:42:41Z
Managing Drug Resistance in Cancer: Role of Cancer Informatics.
Understanding and managing cancer drug resistance is the main goal of the modern oncology programs worldwide. One of the major factors contributing to drug resistance in cancer cells is the acquired mutations in drug targets. Advances in sequencing technologies and high-throughput screening assays have generated huge information related to pharmaco-profiling of anticancer drugs and revealed the mutational spectrum of different cancers. Systematic meta-analysis of this complex data is very essential to make useful conclusions in order to manage cancer drug resistance. Bioinformatics can play a significant role to interpret this complex data into useful conclusions. In this chapter, the use of bioinformatics platforms, particularly CancerDR, in understanding the cancer drug resistance is described.
Ankur Gautam
Kumardeep Chaudhary
Rahul Kumar
Sudheer Gupta
Harinder Singh
G.P.S. Raghava
2019-07-27T09:34:15Z
2019-07-27T11:46:57Z
http://crdd.osdd.net/open/id/eprint/2300
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2300
2019-07-27T09:34:15Z
Structural and functional characterization of an enzyme involved in riboflavin biosynthesis pathway of Helicobacter pylori
Ruchi Gautam
2018-03-26T10:22:28Z
2018-03-26T10:22:28Z
http://crdd.osdd.net/open/id/eprint/1956
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1956
2018-03-26T10:22:28Z
Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India
Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005-2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient's isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen.
Vikas Gautam
Prashant P. Patil
Sunil Kumar
Samriti Midha
Mandeep Kaur
Satinder Kaur
Meenu Singh
Swapna Mali
Jayanthi Shastri
Anita Arora
Pallab Ray
Prabhu B. Patil
2019-08-03T09:32:18Z
2019-08-03T11:46:33Z
http://crdd.osdd.net/open/id/eprint/2319
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2319
2019-08-03T09:32:18Z
Regulation of TIM-3 expression on Dendritic cells
Ravindra Gujar
2016-09-29T10:40:37Z
2016-09-29T10:40:37Z
http://crdd.osdd.net/open/id/eprint/1868
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1868
2016-09-29T10:40:37Z
c-Src Suppresses Dendritic Cell Antitumor Activity via T Cell Ig and Mucin Protein-3 Receptor.
The enhanced expression of T cell Ig and mucin protein-3 (TIM-3) on tumor-associated dendritic cells (DCs) attenuates antitumor effects of DNA vaccines. To identify a potential target (or targets) for reducing TIM-3 expression on tumor-associated DCs, we explored the molecular mechanisms regulating TIM-3 expression. In this study, we have identified a novel signaling pathway (c-Src→Bruton's tyrosine kinase→transcription factors Ets1, Ets2, USF1, and USF2) necessary for TIM-3 upregulation on DCs. Both IL-10 and TGF-β, which are produced in the tumor microenvironment, upregulated TIM-3 expression on DCs via this pathway. Suppressed expression of c-Src or downstream Bruton's tyrosine kinase, Ets1, Ets2, USF1, or USF2 blocked IL-10- and TGF-β-induced TIM-3 upregulation on DCs. Notably, in vivo knockdown of c-Src in mice reduced TIM-3 expression on tumor-associated DCs. Furthermore, adoptive transfer of c-Src-silenced DCs in mouse tumors enhanced the in vivo antitumor effects of immunostimulatory CpG DNA; however, TIM-3 overexpression in c-Src-silenced DCs blocked this effect. Collectively, our data reveal the molecular mechanism regulating TIM-3 expression in DCs and identify c-Src as a target for improving the efficacy of nucleic acid-mediated anticancer therapy.
Ravindra Gujar
Neeraj Maurya
Vinod Yadav
Mamta Gupta
Saurabh Arora
Neeraj Khatri
Pradip Sen
2016-09-29T10:36:57Z
2016-09-29T10:36:57Z
http://crdd.osdd.net/open/id/eprint/1869
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1869
2016-09-29T10:36:57Z
ZikaVR: An Integrated Zika Virus Resource for Genomics, Proteomics, Phylogenetic and Therapeutic Analysis.
Current Zika virus (ZIKV) outbreaks that spread in several areas of Africa, Southeast Asia, and in pacific islands is declared as a global health emergency by World Health Organization (WHO). It causes Zika fever and illness ranging from severe autoimmune to neurological complications in humans. To facilitate research on this virus, we have developed an integrative multi-omics platform; ZikaVR (http://bioinfo.imtech.res.in/manojk/zikavr/), dedicated to the ZIKV genomic, proteomic and therapeutic knowledge. It comprises of whole genome sequences, their respective functional information regarding proteins, genes, and structural content. Additionally, it also delivers sophisticated analysis such as whole-genome alignments, conservation and variation, CpG islands, codon context, usage bias and phylogenetic inferences at whole genome and proteome level with user-friendly visual environment. Further, glycosylation sites and molecular diagnostic primers were also analyzed. Most importantly, we also proposed potential therapeutically imperative constituents namely vaccine epitopes, siRNAs, miRNAs, sgRNAs and repurposing drug candidates.
Amit Kumar Gupta
Karambir Kaur
Akanksha Rajput
Sandeep Kumar Dhanda
Manika Sehgal
Md Shoaib Khan
Isha Monga
Showkat Ahmad Dar
Sandeep Singh
Gandharva Nagpal
Salman Sadullah Usmani
Anamika Thakur
Gazaldeep Kaur
Shivangi Sharma
Aman Bhardwaj
Abid Qureshi
G.P.S. Raghava
Manoj Kumar
2016-09-29T10:34:44Z
2016-09-29T10:34:44Z
http://crdd.osdd.net/open/id/eprint/1870
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1870
2016-09-29T10:34:44Z
Prioritization of anticancer drugs against a cancer using genomic features of cancer cells: A step towards personalized medicine.
In this study, we investigated drug profile of 24 anticancer drugs tested against a large number of cell lines in order to understand the relation between drug resistance and altered genomic features of a cancer cell line. We detected frequent mutations, high expression and high copy number variations of certain genes in both drug resistant cell lines and sensitive cell lines. It was observed that a few drugs, like Panobinostat, are effective against almost all types of cell lines, whereas certain drugs are effective against only a limited type of cell lines. Tissue-specific preference of drugs was also seen where a drug is more effective against cell lines belonging to a specific tissue. Genomic features based models have been developed for each anticancer drug and achieved average correlation between predicted and actual growth inhibition of cell lines in the range of 0.43 to 0.78. We hope, our study will throw light in the field of personalized medicine, particularly in designing patient-specific anticancer drugs. In order to serve the scientific community, a webserver, CancerDP, has been developed for predicting priority/potency of an anticancer drug against a cancer cell line using its genomic features (http://crdd.osdd.net/raghava/cancerdp/).
Sudheer Gupta
Kumardeep Chaudhary
Rahul Kumar
Ankur Gautam
Jagpreet Singh Nanda
Sandeep Kumar Dhanda
Samir Kumar Brahmachari
G.P.S. Raghava
2019-07-27T10:16:47Z
2019-07-27T11:58:18Z
http://crdd.osdd.net/open/id/eprint/2309
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2309
2019-07-27T10:16:47Z
Studies on the process optimization for Biosurfactant production and its application Development
Farazul Haque
2016-09-29T10:32:25Z
2016-09-29T10:32:25Z
http://crdd.osdd.net/open/id/eprint/1871
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1871
2016-09-29T10:32:25Z
Inhibitory Effect of Sophorolipid on Candida albicans Biofilm Formation and Hyphal Growth.
Candida albicans causes superficial and life-threatening systemic infections. These are difficult to treat often due to drug resistance, particularly because C. albicans biofilms are inherently resistant to most antifungals. Sophorolipid (SL), a glycolipid biosurfactant, has been shown to have antimicrobial and anticancer properties. In this study, we investigated the effect of SL on C. albicans biofilm formation and preformed biofilms. SL was found to inhibit C. albicans biofilm formation as well as reduce the viability of preformed biofilms. Moreover, SL, when used along with amphotericin B (AmB) or fluconazole (FLZ), was found to act synergistically against biofilm formation and preformed biofilms. Effect of SL on C. albicans biofilm formation was further visualized by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), which revealed absence of hyphae, typical biofilm architecture and alteration in the morphology of biofilm cells. We also found that SL downregulates the expression of hypha specific genes HWP1, ALS1, ALS3, ECE1 and SAP4, which possibly explains the inhibitory effect of SL on hyphae and biofilm formation.
Farazul Haque
Md Alfatah
K Ganesan
Mani Shankar Bhattacharyya
2016-09-29T10:24:33Z
2016-09-29T10:24:33Z
http://crdd.osdd.net/open/id/eprint/1873
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1873
2016-09-29T10:24:33Z
β-Endorphin enhances the phospholipase activity of the dandruff causing fungi Malassezia globosa and Malassezia restricta.
β-Endorphin is known to stimulate phospholipase production by Malassezia pachydermatis during canine dermatoses. The role of β-endorphin in Malassezia infection in humans is not well studied. The present study compares the influence of β-endorphin on Malassezia globosa and Malassezia restricta isolated from patients with seborrhoeic dermatitis/dandruff (SD/D) and healthy controls. Malassezia isolates (five each of the two species from patients and healthy controls) were grown on modified Dixon's agar with or without 100 nmol/L β-endorphin. Phospholipase activity was quantified based on its ability to hydrolyze L-α-phosphatidylcholine dimyristoyl (phospholipid substrate). Free fatty acid was measured by a colorimetry method. In isolates from patients, the phospholipase activity significantly increased after exposure to β-endorphin (M. globosa, P = .04; M. restricta, P = .001), which did not occur in isolates from healthy controls. Moreover, after β-endorphin exposure the patient isolates had significantly higher (P = .0004) phospholipase activity compared to the healthy control isolates. The results suggest that isolates of M. globosa and M. restricta from patients may differ from those of healthy humans.
Prasanna Honnavar
Arunaloke Chakrabarti
Ghandam S Prasad
Pankaj Singh
Sunil Dogra
Shivaprakash M Rudramurthy
2016-09-29T10:27:07Z
2016-09-29T10:27:07Z
http://crdd.osdd.net/open/id/eprint/1872
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1872
2016-09-29T10:27:07Z
Malassezia arunalokei sp. nov., a Novel Yeast Species Isolated from Seborrheic Dermatitis Patients and Healthy Individuals from India.
The majority of species within the genus Malassezia are lipophilic yeasts that colonize the skin of warm-blooded animals. Two species, Malassezia globosa and Malassezia restricta, are implicated in the causation of seborrheic dermatitis/dandruff (SD/D). During our survey of SD/D cases, we isolated several species of Malassezia and noticed vast variations within a few lipid-dependent species. Variations observed in the phenotypic characteristics (colony morphology, absence of catalase activity, growth at 37°C, and precipitation surrounding wells containing Tween 20 or Cremophor EL) suggested the possible presence of a novel species. Sequence divergence observed in the internal transcribed spacer (ITS) region, the D1/D2 domain, and the intergenic spacer 1 (IGS1) region of rDNA and the TEF1 gene, PCR-restriction fragment length polymorphism (RFLP) analysis of the ITS2 region, and fluorescent amplified fragment length polymorphism analysis support the existence of a novel species. Based on phenotypic and molecular characterization of these strains, we propose a new species, namely, M. arunalokei sp. nov., and we designate NCCPF 127130 (= MTCC 12054 = CBS 13387) as the type strain.
Prasanna Honnavar
Gandham S Prasad
Anup Ghosh
Sunil Dogra
Sanjeev Handa
Shivaprakash M Rudramurthy
2016-09-29T10:16:53Z
2016-09-29T10:16:53Z
http://crdd.osdd.net/open/id/eprint/1874
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1874
2016-09-29T10:16:53Z
Functional inhibition of Hsp70 by Pifithrin-μ switches Gambogic acid induced caspase dependent cell death to caspase independent cell death in human bladder cancer cells.
Heat shock protein-70kDa (Hsp70) is a member of molecular chaperone family, involved in the proper folding of various proteins. Hsp70 is important for tumor cell survival and is also reported to be involved in enhancing the drug resistance of various cancer types. Hsp70 controls apoptosis both upstream and downstream of the mitochondria by regulating the mitochondrial membrane permeabilization (MMP) and apoptosome formation respectively. In the present study, we have elucidated the role of Hsp70 in Gambogic acid (GA) induced apoptosis in bladder cancer cells. We observed that functional inhibition of Hsp70 by Pifithrin-μ switches GA induced caspase dependent (apoptotic) cell death to caspase independent cell death. However, this cell death was not essentially necrotic in nature, as shown by the observations like intact plasma membranes, cytochrome-c release and no significant effect on nuclear condensation/fragmentation. Inhibition of Hsp70 by Pifithrin-μ shows differential effect on MMP. GA induced MMP and cytochrome-c release was inhibited by Pifithrin-μ at 12h but enhanced at 24h. Pifithrin-μ also reverted back GA inhibited autophagy which resulted in the degradation of accumulated ubiquitinated proteins. Our results demonstrate that Hsp70 plays an important role in GA induced apoptosis by regulating caspase activation. Therefore, inhibition of Hsp70 may hamper with the caspase dependent apoptotic pathways induced by most anti-cancer drugs and reduce their efficacy. However, the combination therapy with Pifithrin-μ may be particularly useful in targeting apoptotic resistant cancer cells as Pifithrin-μ may initiate alternative cell death program in these resistant cells.
Mohammad Ishaq
Rani Ojha
Kapil Sharma
Gaurav Sharma
Shrawan K Singh
Sekhar Majumdar
2016-09-29T10:13:57Z
2016-09-29T10:13:57Z
http://crdd.osdd.net/open/id/eprint/1875
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1875
2016-09-29T10:13:57Z
Molecular dynamics simulations show altered secondary structure of clawless in binary complex with DNA providing insights into aristaless-clawless-DNA ternary complex formation.
Aristaless (Al) and clawless (Cll) homeodomains that are involved in leg development in Drosophila melanogaster are known to bind cooperatively to 5'-(T/C)TAATTAA(T/A)(T/A)G-3' DNA sequence, but the mechanism of their binding to DNA is unknown. Molecular dynamics (MD) studies have been carried out on binary, ternary, and reconstructed protein-DNA complexes involving Al, Cll, and DNA along with binding free energy analysis of these complexes. Analysis of MD trajectories of Cll-3A01, binary complex reveals that C-terminal end of helixIII of Cll, unwind in the absence of Al and remains so in reconstructed ternary complex, Cll-3A01-Al. In addition, this change in secondary structure of Cll does not allow it to form protein-protein interactions with Al in the ternary reconstructed complex. However, secondary structure of Cll and its interactions are maintained in other reconstructed ternary complex, Al-3A01-Cll where Cll binds to Al-3A01, binary complex to form ternary complex. These interactions as observed during MD simulations compare well with those observed in ternary crystal structure. Thus, this study highlights the role of helixIII of Cll and protein-protein interactions while proposing likely mechanism of recognition in ternary complex, Al-Cll-DNA.
Sangita Kachhap
Pragya Priyadarshini
Balvinder Singh
2016-09-29T09:55:23Z
2016-09-29T09:55:23Z
http://crdd.osdd.net/open/id/eprint/1876
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1876
2016-09-29T09:55:23Z
Dual Role of a Biosynthetic Enzyme, CysK, in Contact Dependent Growth Inhibition in Bacteria.
Contact dependent growth inhibition (CDI) is the phenomenon where CDI+ bacterial strain (inhibitor) inhibits the growth of CDI-strain (target) by direct cell to cell contact. CDI is mediated by cdiBAI gene cluster where CdiB facilitates the export of CdiA, an exotoxin, on the cell surface and CdiI acts as an immunity protein to protect CDI+ cells from autoinhibition. CdiA-CT, the C-terminal region of the toxin CdiA, from uropathogenic Escherichia coli strain 536 (UPEC536) is a latent tRNase that requires binding of a biosynthetic enzyme CysK (O-acetylserine sulfyhydrylase) for activation in the target cells. CdiA-CT can also interact simultaneously with CysK and immunity protein, CdiI, to form a ternary complex in UPEC536. But the role of CysK in the ternary complex is not clear. We studied the hydrodynamic, thermodynamic and kinetic parameters of binary and ternary complexes using AUC, ITC and SPR respectively, to investigate the role of CysK in UPEC536. We report that CdiA-CT binds CdiI and CysK with nanomolar range affinity. We further report that binding of CysK to CdiA-CT improves its affinity towards CdiI by ~40 fold resulting in the formation of a more stable complex with over ~130 fold decrease in dissociation rate. Thermal melting experiments also suggest the role of CysK in stabilizing CdiA-CT/CdiI complex as Tm of the binary complex shifts ~10°C upon binding CysK. Hence, CysK acts a modulator of CdiA-CT/CdiI interactions by stabilizing CdiA-CT/CdiI complex and may play a crucial role in preventing autoinhibition in UPEC536. This study reports a new moonlighting function of a biosynthetic enzyme, CysK, as a modulator of toxin/immunity interactions in UPEC536 inhibitor cells.
Soni Kaundal
Manju Uttam
Krishan Gopal Thakur
2018-03-28T05:26:11Z
2018-03-28T05:26:11Z
http://crdd.osdd.net/open/id/eprint/2055
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2055
2018-03-28T05:26:11Z
ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione
Glutathione degradation plays an important role in glutathione and redox homeostasis, and thus it is imperative to understand the enzymes and the mechanisms involved in glutathione degradation in detail. We describe here ChaC2, a member of the ChaC family of γ-glutamylcyclotransferases, as an enzyme that degrades glutathione in the cytosol of mammalian cells. ChaC2 is distinct from the previously described ChaC1, to which ChaC2 shows ∼50% sequence identity. Human and mouse ChaC2 proteins purified in vitro show 10-20-fold lower catalytic efficiency than ChaC1, although they showed comparable Km values (Km of 3.7 ± 0.4 mm and kcat of 15.9 ± 1.0 min-1 toward glutathione for human ChaC2; Km of 2.2 ± 0.4 mm and kcat of 225.2 ± 15 min-1 toward glutathione for human ChaC1). The ChaC1 and ChaC2 proteins also shared the same specificity for reduced glutathione, with no activity against either γ-glutamyl amino acids or oxidized glutathione. The ChaC2 proteins were found to be expressed constitutively in cells, unlike the tightly regulated ChaC1. Moreover, lower eukaryotes have a single member of the ChaC family that appears to be orthologous to ChaC2. In addition, we determined the crystal structure of yeast ChaC2 homologue, GCG1, at 1.34 Å resolution, which represents the first structure of the ChaC family of proteins. The catalytic site is defined by a fortuitous benzoic acid molecule bound to the crystal structure. The mechanism for binding and catalytic activity of this new enzyme of glutathione degradation, which is involved in continuous but basal turnover of cytosolic glutathione, is proposed.
Amandeep Kaur
Ruchi Gautam
Ritika Srivastava
Avinash Chandel
Akhilesh Kumar
Subramanian Karthikeyan
Anand Kumar Bachhawat
2016-09-29T09:49:50Z
2016-09-29T09:49:50Z
http://crdd.osdd.net/open/id/eprint/1878
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1878
2016-09-29T09:49:50Z
Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution.
Treble clef (TC) zinc fingers constitute a large fold-group of structural zinc-binding protein domains that mediate numerous cellular functions. We have analysed the sequence, structure, and function relationships among all TCs in the Protein Data Bank. This led to the identification of novel TCs, such as lsr2, YggX and TFIIIC τ 60 kDa subunit, and prediction of a nuclease-like function for the DUF1364 family. The structural malleability of TCs is evident from the many examples with variations to the core structural elements of the fold. We observe domains wherein the structural core of the TC fold is circularly permuted, and also some examples where the overall fold resembles both the TC motif and another unrelated fold. All extant TC families do not share a monophyletic origin, as several TC proteins are known to have been present in the last universal common ancestor and the last eukaryotic common ancestor. We identify several TCs where the zinc-chelating site and residues are not merely responsible for structure stabilization but also perform other functions, such as being redox active in C1B domain of protein kinase C, a nucleophilic acceptor in Ada and catalytic in organomercurial lyase, MerB.
Gurmeet Kaur
Srikrishna Subramanian
2018-03-26T09:52:54Z
2018-03-26T09:52:54Z
http://crdd.osdd.net/open/id/eprint/1965
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1965
2018-03-26T09:52:54Z
Genome sequencing, assembly, annotation and analysis of Staphylococcus xylosus strain DMB3-Bh1 reveals genes responsible for pathogenicity
BACKGROUND:
Staphylococcus xylosus is coagulase-negative staphylococci (CNS), found occasionally on the skin of humans but recurrently on other mammals. Recent reports suggest that this commensal bacterium may cause diseases in humans and other animals. In this study, we present the first report of whole genome sequencing of S. xylosus strain DMB3-Bh1, which was isolated from the stool of a mouse.
RESULTS:
The draft genome of S. xylosus strain DMB3-Bh1 consisted of 2,81,0255 bp with G+C content of 32.7 mol%, 2623 predicted coding sequences (CDSs) and 58 RNAs. The final assembly contained 12 contigs of total size 2,81,0255 bp with N50 contig length of 4,37,962 bp and the largest contig assembled measured 7,61,338 bp. Further, an interspecies comparative genomic analysis through rapid annotation using subsystem technology server was achieved with Staphylococcus aureus RF122 that revealed 36 genes having similarity with S. xylosus DMB3-Bh1. 35 genes encoded for virulence, disease and defense and 1 gene encoded for phages, prophages and transposable elements.
CONCLUSIONS:
These results suggest co linearity in genes between S. xylosus DMB3-Bh1 and S. aureus RF122 that contribute to pathogenicity and might be the result of horizontal gene transfer. The study indicates that S. xylosus DMB3-Bh1 may be a potential emerging pathogen for rodents.
Gurwinder Kaur
Amit Arora
Sathyaseelan Sathyabama
Nida Mubin
Sheenam Verma
Shanmugam Mayilraj
J N Agrewala
2016-09-29T09:42:32Z
2018-10-31T06:09:37Z
http://crdd.osdd.net/open/id/eprint/1879
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1879
2016-09-29T09:42:32Z
Brachybacterium aquaticum sp. nov., a novel actinobacterium isolated from sea water.
A pale-yellowish bacterium, strain KWS-1T, was isolated from sea water during a study of the bacterial diversity of marine environment of Kanyakumari coastal region of Bay of Bengal, India and was studied by using a polyphasic taxonomic approach. The strain KWS-1T had morphological and chemotaxonomic properties (cell-wall diamino acid, menaquinone and fatty acid profile) consistent with its classification in the genus Brachybacterium. Phylogenetic analysis of the 16S rRNA gene sequence showed that strain KWS-1T was closely related to Brachybacterium paraconglomeratum JCM 17781T, followed by Brachybacterium saurashtrense DSM 23186T, Brachybacterium gingengisoli JCM 19356T, Brachybacterium faecium JCM 11609T and Brachybacterium conglomeratum JCM 11608T (98.45, 98.24, 98.12, 98.10 and 98.10% sequence similarity, respectively), whereas the sequence similarity values with respect to the other Brachybacterium species with validly published names were between 97.4 and 94.2%. However, the DNA-DNA hybridization of strain KWS-1T and other five closely related species were less than the thresh hold value. The major lipids are diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and phosphatidylserine (PS) and quinone is MK-7. The DNA G+C content of the strain is 71.8 mol%. The above data in combination with the phenotypic distinctiveness of KWS-1T with other reference strains clearly indicate that the strain represents a novel species, for which the name Brachybacterium aquaticum sp. nov. is proposed. The type strain is KWS-1T (= MTCC 11836T = DSM 28796T = JCM 30059T).
Gurwinder Kaur
Narender Kumar
Poonam Mual
Anand Kumar
Rajendran Mathan Kumar
Shanmugam Mayilraj
2018-03-26T09:50:37Z
2018-03-26T09:50:37Z
http://crdd.osdd.net/open/id/eprint/1999
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1999
2018-03-26T09:50:37Z
Microbacterium aureliae sp. nov., a novel actinobacterium isolated from Aurelia aurita, the moon jellyfish
The taxonomic position of a lemon-yellow-pigmented actinobacterium, strain JF-6T, isolated from Aurelia aurita, the moon jellyfish, collected from the Bay of Bengal coast, Kanyakumari, India, was determined using a polyphasic approach. The strain had phenotypic and chemotaxonomic properties that were consistent with its classification in the genus Microbacterium. Alignment of the 16S rRNA gene sequence of strain JF-6T with sequences from Microbacterium arthrosphaerae CC-VM-YT, Microbacterium yannicii G72T, Microbacterium trichothecenolyticum IFO 15077T, Microbacterium flavescens DSM 20643T, Microbacterium insulae DS-66T, Microbacterium resistens DMMZ 1710T and Microbacterium thalassium IFO 16060T revealed similarities of 98.95, 98.76, 98.43, 98.41, 98.41, 98.26 and 98.22 %, respectively. However, the levels of DNA-DNA relatedness with its closest phylogenetic neighbours confirmed that it represents a novel species within the genus. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and an unknown glycolipid. The major menaquinones detected for strain JF-6T were MK-13 and MK-12. The diamino acid in the cell-wall peptidoglycan was ornithine and the peptidoglycan was type B2β (Glu/Hyg-Gly-d-Orn). The DNA G+C content was 69.4 mol%. Based on these differences, strain JF-6T (=MTCC 11843T=JCM 30060T=KCTC 39828T) should be classified as the type strain of a novel species of Microbacterium, for which the name Microbacterium aureliae sp. nov. is proposed.
Gurwinder Kaur
Parveen Mual
Narender Kumar
Ashish Verma
Anand Kumar
Srinivasan Krishnamurthi
Shanmugam Mayilraj
2016-10-04T06:23:47Z
2016-10-04T06:23:47Z
http://crdd.osdd.net/open/id/eprint/1917
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1917
2016-10-04T06:23:47Z
ge-CRISPR - An integrated pipeline for the prediction and analysis of sgRNAs genome editing efficiency for CRISPR/Cas system.
Genome editing by sgRNA a component of CRISPR/Cas system emerged as a preferred technology for genome editing in recent years. However, activity and stability of sgRNA in genome targeting is greatly influenced by its sequence features. In this endeavor, a few prediction tools have been developed to design effective sgRNAs but these methods have their own limitations. Therefore, we have developed "ge-CRISPR" using high throughput data for the prediction and analysis of sgRNAs genome editing efficiency. Predictive models were employed using SVM for developing pipeline-1 (classification) and pipeline-2 (regression) using 2090 and 4139 experimentally verified sgRNAs respectively from Homo sapiens, Mus musculus, Danio rerio and Xenopus tropicalis. During 10-fold cross validation we have achieved accuracy and Matthew's correlation coefficient of 87.70% and 0.75 for pipeline-1 on training dataset (T(1840)) while it performed equally well on independent dataset (V(250)). In pipeline-2 we attained Pearson correlation coefficient of 0.68 and 0.69 using best models on training (T(3169)) and independent dataset (V(520)) correspondingly. ge-CRISPR (http://bioinfo.imtech.res.in/manojk/gecrispr/) for a given genomic region will identify potent sgRNAs, their qualitative as well as quantitative efficiencies along with potential off-targets. It will be useful to scientific community engaged in CRISPR research and therapeutics development.
Karambir Kaur
Amit Kumar Gupta
Akanksha Rajput
Manoj Kumar
2016-10-04T05:54:48Z
2016-10-04T05:54:48Z
http://crdd.osdd.net/open/id/eprint/1916
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1916
2016-10-04T05:54:48Z
Novel mutations conferring resistance to kanamycin in Mycobacterium tuberculosis clinical isolates from Northern India.
Twenty-nine Kanamycin resistant clinical isolates of Mycobacterium tuberculosis from Northern India were screened to evaluate genetic mutations in rrs gene, eis gene with its promoter, and whiB7 gene along with its 5'UTR. 14 strains (~48.0%) collectively exhibited mutations in rrs, eis or whiB7 target regions. While the highest frequency of mutations was found in rrs gene, eis and whiB7 loci displayed novel mutations. The novel mutations displayed by eis and whiB7 loci were found to be associated specifically with the Kanamycin resistance as none of the twenty nine Kanamycin sensitive strains harbor them. The inclusion of novel mutations of eis and whiB7 loci will be useful in improving the specificity of future diagnostics.
Simerpreet Kaur
Vibhuti Rana
Pooja Singh
Garima Trivedi
Shashi Anand
Amanpreet Kaur
Pawan Gupta
Amita Jain
Charu Sharma
2016-10-04T06:12:18Z
2016-10-04T06:12:18Z
http://crdd.osdd.net/open/id/eprint/1920
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1920
2016-10-04T06:12:18Z
ViralEpi v1.0: a high-throughput spectrum of viral epigenomic methylation profiles from diverse diseases.
To develop a computational resource for viral epigenomic methylation profiles from diverse diseases.
Mohd Shoaib Khan
Amit Kumar Gupta
Manoj Kumar
2016-09-29T09:36:09Z
2016-09-29T09:36:09Z
http://crdd.osdd.net/open/id/eprint/1881
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1881
2016-09-29T09:36:09Z
Triggering through NOD-2 Differentiates Bone Marrow Precursors to Dendritic Cells with Potent Bactericidal activity.
Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naïve T cells. The role of pattern recognition receptors like Toll-Like Receptors and Nod-Like Receptors expressed on DCs is well-defined in the recognition of the pathogens. However, nothing is precisely studied regarding the impact of NOD-2 signaling during the differentiation of DCs. Consequently, we explored the role of NOD-2 signaling in the differentiation of DCs and therefore their capability to activate innate and adaptive immunity. Intriguingly, we observed that NOD-2 stimulated DCs (nDCs) acquired highly activated and matured phenotype and exhibited substantially greater bactericidal activity by robust production of nitric oxide. The mechanism involved in improving the functionality of nDCs was dependent on IFN-αβ signaling, leading to the activation of STAT pathways. Furthermore, we also observed that STAT-1 and STAT-4 dependent maturation and activation of DCs was under the feedback mechanism of SOCS-1 and SOCS-3 proteins. nDCs acquired enhanced potential to activate chiefly Th1 and Th17 immunity. Taken together, these results suggest that nDCs can be exploited as an immunotherapeutic agent in bolstering host immunity and imparting protection against the pathogens.
Nargis Khan
Mohammad Aqdas
Aurobind Vidyarthi
Shikha Negi
Susanta Pahari
Tapan Agnihotri
J N Agrewala
2016-10-20T04:54:26Z
2016-10-20T04:54:26Z
http://crdd.osdd.net/open/id/eprint/1923
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1923
2016-10-20T04:54:26Z
Stimulation through CD40 and TLR-4 Is an Effective Host Directed Therapy against Mycobacterium tuberculosis.
Tuberculosis (TB) is the leading cause of morbidity and mortality among all infectious diseases. Failure of Bacillus Calmette Guerin as a vaccine and serious side-effects and toxicity due to long-term TB drug regime are the major hurdles associated with TB control. The problem is further compounded by the emergence of drug-resistance strains of Mycobacterium tuberculosis (Mtb). Consequently, it demands a serious attempt to explore safer and superior treatment approaches. Recently, an improved understanding of host-pathogen interaction has opened up new avenues for immunotherapy for treating TB. Although, dendritic cells (DCs) show a profound role in generating immunity against Mtb, their immunotherapeutic potential needs to be precisely investigated in controlling TB. Here, we have devised an approach of bolstering DCs efficacy against Mtb by delivering signals through CD40 and TLR-4 molecules. We found that DCs triggered through CD40 and TLR-4 showed increased secretion of IL-12, IL-6, and TNF-α. It also augmented autophagy. Interestingly, CD40 and TLR-4 stimulation along with the suboptimal dose of anti-TB drugs significantly fortified their efficacy to kill Mtb. Importantly, animals treated with the agonists of CD40 and TLR-4 boosted Th1 and Th17 immunity. Furthermore, it amplified the pool of memory CD4 T cells as well as CD8 T cells. Furthermore, substantial reduction in the bacterial burden in the lungs was observed. Notably, this adjunct therapy employing immunomodulators and chemotherapy can reinvigorate host immunity suppressed due to drugs and Mtb. Moreover, it would strengthen the potency of drugs in curing TB.
Nargis Khan
Susanta Pahari
Aurobind Vidyarthi
Mohammad Aqdas
Javed N Agrewala
2018-03-24T04:39:05Z
2018-11-05T10:03:37Z
http://crdd.osdd.net/open/id/eprint/1967
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1967
2018-03-24T04:39:05Z
T-cell exhaustion in tuberculosis: pitfalls and prospects
T-cells play an important role in immunity but when these cells are overexposed to specific antigens, their function may decline. This state is usually referred to as exhaustion and the T-cells show reduced proliferation and functions such as cytokine release. T-cell exhaustion has been observed in several cancers as well as in chronic infections such as tuberculosis (TB). In chronic Mycobacterium tuberculosis (Mtb) infection, T-cells may express the exhaustion phenotype and show a progressive loss of secretion of IL-2, IFN-γ and TNF-α. In some cancers and chronic infection models, blocking the exhaustion phenotype can be achieved with the so-called checkpoint inhibitors. This results in tumor control and more effective immunity. However, in the case of TB, the T-cell exhaustion results are quite ambiguous. Hence, there is a need to investigate and explain the contribution of checkpoint at a molecular level to the outcome of events in chronic TB. Such information could help to guide the success of new therapies against chronic TB. This review highlights the mechanism through which T-cells undergo exhaustion and the approaches that can avert such events. This will help to design immunotherapies that can reinvigorate T-cell potency to protect patients from TB.
Nargis Khan
Aurobind Vidyarthi
Mohammed Amir
Khurram Mushtaq
Javed Naim Agrewala
2016-03-11T09:00:53Z
2016-03-11T09:02:12Z
http://crdd.osdd.net/open/id/eprint/1845
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1845
2016-03-11T09:00:53Z
Innate immunity holding the flanks until reinforced by adaptive immunity against Mycobacterium tuberculosis infection
T cells play a cardinal role in imparting adaptive immunity against Mycobacterium tuberculosis (Mtb). However, ample time is required before T-cells are able to evoke efficient effector responses in the lung, where the mycobacterium inflicts disease. This delay in T cells priming, which is termed as lag phase, provides sufficient time for Mtb to replicate and establish itself within the host. In contrast, innate immunity efficiently curb the growth of Mtb during initial phase of infection through several mechanisms. Pathogen recognition by innate cells rapidly triggers a cascade of events, such as apoptosis, autophagy, inflammasome formation and nitric oxide production to kill intracellular pathogens. Furthermore, bactericidal mechanisms such as autophagy and apoptosis, augment the antigen processing and presentation, thereby contributing substantially to the induction of adaptive immunity. This manuscript highlights the role of innate immune mechanisms in restricting the survival of Mtb during lag phase. Finally, this article provides new insight for designing immuno-therapies by targeting innate immune mechanisms to achieve optimum immune response to cure TB.
Nargis Khan
Aurobind Vidyarthi
Shifa Javed
J N Agrewala
2016-11-11T04:24:44Z
2018-04-02T08:02:05Z
http://crdd.osdd.net/open/id/eprint/1924
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1924
2016-11-11T04:24:44Z
Alteration in the gut microbiota provokes susceptibility to tuberculosis
The microbiota that resides in the gastrointestinal tract provides essential health benefits to the host. In particular, they regulate immune homeostasis. Recently, several evidences indicate that alteration in the gut microbial community can cause infectious and non-infectious diseases. Tuberculosis (TB) is the most devastating disease, inflicting mortality and morbidity. It remains unexplored, whether changes in the gut microbiota can provoke or prevent TB. In the current study, we have demonstrated the antibiotics driven changes in the gut microbial composition and their impact on the survival of Mtb in the lungs, liver and spleen of infected mice, compared to those with intact microbiota. Interestingly, dysbiosis of microbes showed significant increase in the bacterial burden in lungs and dissemination of Mtb to spleen and liver. Further, elevation in the number of Tregs and decline in the pool of IFN-γ and TNF-α releasing CD4 T cells was noticed. Interestingly, fecal transplantation in the gut microbiota disrupted animals exhibited improved Th1 immunity and lesser Tregs population. Importantly, these animals displayed reduced severity to Mtb infection. This study for the first time demonstrated the novel role of gut microbes in the susceptibility to TB and its prevention by microbial implants. In future, microbial therapies may help in treating patients suffering from TB.
Nargis Khan
Aurobind Vidyarthi
Sajid Nadeem
Shikha Negi
Girish Nair
J N Agrewala
2016-02-01T13:00:26Z
2016-02-01T13:00:26Z
http://crdd.osdd.net/open/id/eprint/1812
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1812
2016-02-01T13:00:26Z
Signaling through NOD-2 and TLR-4 Bolsters the T cell Priming Capability of Dendritic cells by Inducing Autophagy.
T cells play a cardinal role in mediating protection against intracellular pathogens like Mycobacterium tuberculosis (Mtb). It is important to understand the factors that govern the T cell response; thereby can modulate its activity. Dendritic cells (DCs) are the major player in initiation and augmentation of T cell response. Targeting DCs to induce their optimum maturation and activation can lead to a better T cell response. Interestingly, we observed that combinatorial signaling of DCs through NOD-2 and TLR-4 fortified better yield of IL-12p40/70, IL-6 and IFN-γ and upregulated the expression of CD40, CD80 and CD86 costimulatory molecules. Further, we noticed improved phagocytic capabilities of DCs. Furthermore, NOD-2 and TLR-4 induced autophagy in DCs, which enhanced the activation of T cells. This study signifies that NOD-2 and TLR-4 exhibit synergism in invigorating the activity of DCs. Consequently, this strategy may have significant immunotherapeutic potential in bolstering the function of DCs and thus improving the immunity against pathogens.
Nargis Khan
Aurobind Vidyarthi
Susanta Pahari
Shikha Negi
Mohammad Aqdas
Sajid Nadeem
Tapan Agnihotri
J N Agrewala
2019-07-27T09:14:54Z
2019-07-27T11:41:50Z
http://crdd.osdd.net/open/id/eprint/2296
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2296
2019-07-27T09:14:54Z
Genomics enabled Microbial Systematics
Indu Khatri
2016-09-29T09:28:36Z
2016-09-29T09:28:36Z
http://crdd.osdd.net/open/id/eprint/1882
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1882
2016-09-29T09:28:36Z
Complete Genomes of Bacillus coagulans S-lac and Bacillus subtilis TO-A JPC, Two Phylogenetically Distinct Probiotics.
Several spore-forming strains of Bacillus are marketed as probiotics due to their ability to survive harsh gastrointestinal conditions and confer health benefits to the host. We report the complete genomes of two commercially available probiotics, Bacillus coagulans S-lac and Bacillus subtilis TO-A JPC, and compare them with the genomes of other Bacillus and Lactobacillus. The taxonomic position of both organisms was established with a maximum-likelihood tree based on twenty six housekeeping proteins. Analysis of all probiotic strains of Bacillus and Lactobacillus reveal that the essential sporulation proteins are conserved in all Bacillus probiotic strains while they are absent in Lactobacillus spp. We identified various antibiotic resistance, stress-related, and adhesion-related domains in these organisms, which likely provide support in exerting probiotic action by enabling adhesion to host epithelial cells and survival during antibiotic treatment and harsh conditions.
Indu Khatri
Shailza Sharma
T N C Ramya
Srikrishna Subramanian
2016-09-29T09:24:04Z
2016-09-29T09:24:04Z
http://crdd.osdd.net/open/id/eprint/1883
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1883
2016-09-29T09:24:04Z
Novosphingobium pokkalii sp nov, a novel rhizosphere-associated bacterium with plant beneficial properties isolated from saline-tolerant pokkali rice.
Pokkali rice varieties are known for their saline tolerance when specifically grown in coastal saline affected agri-fields of southern Kerala. These fields are prone to seawater intrusion. During characterization of phytobeneficial rhizobacteria from this pokkali rice, L3E4(T) was isolated. This strain showed some plant growth-promoting functions (production of indole acetic acid (IAA), acetoin, and siderophore), biofilm formation and the capacity for use of a wide range of plant-derived organic compounds. In planta assay under axenic conditions showed a positive effect of L3E4(T) on pokkali rice growth; importantly, it was able to attach and colonize pokkali rice roots in the presence of natural seawater, a key adaptation required for survival in pokkali rice fields. Phylogenetic analysis using 16S rRNA, recA, and gyrB gene sequences showed that strain L3E4(T) belongs to the genus Novosphingobium, with Novosphingobium capsulatum GIFU 11526(T) and Novosphingobium rhizosphaerae JM.1(T) being the nearest phylogenetic relatives. In addition, DNA-DNA hybridization analysis and phenotypic traits established that this strain belongs to a novel Novosphingobium species, for which we propose the name Novosphingobium pokkalii sp. nov. The type strain is represented by strain L3E4(T) (=MTCC 12357(T) = KCTC 42224(T)).
Ramya Krishnan
Rahul R Menon
. Likhitha
Hans-Jürgen Busse
Naoto Tanaka
Srinivasan Krishnamurthi
N Rameshkumar
2019-08-03T09:36:07Z
2019-08-03T11:47:35Z
http://crdd.osdd.net/open/id/eprint/2320
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2320
2019-08-03T09:36:07Z
Identification of molecular component(s) in malaria parasite and infected cells having therapeutic an diagnostic potential
Binod Kumar
2019-07-27T10:09:39Z
2019-07-27T11:56:15Z
http://crdd.osdd.net/open/id/eprint/2307
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2307
2019-07-27T10:09:39Z
Molecular Insight into the Role of Cellular Chaperone Machinery in Yeast Prion Propagation
Navinder Kumar
2018-03-24T04:21:21Z
2018-03-24T04:21:21Z
http://crdd.osdd.net/open/id/eprint/1972
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1972
2018-03-24T04:21:21Z
Facile synthesis, structural evaluation, antimicrobial activity and synergistic effects of novel imidazo[1,2-a]pyridine based organoselenium compounds
A simple and efficient method has been described to synthesize the hitherto unknown imidazo[1,2-a]pyridine selenides (5a-l) by reaction of 2-chloroimidazo [1,2-a]pyridines with aryl/heteroaryl selenols, generated in situ by reduction of various diselenides with hypophosphorous acid. The crystal structures of 3-nitro-2-(phenylselanyl)-imidazo[1,2-a]pyridine (5a), 2-(mesitylselanyl)-3-nitro-imidazo[1,2-a]pyridine (5d) and 3-nitro-2-(pyridin-2-ylselanyl)-imidazo[1,2-a]pyridine (5e) were confirmed by X-ray crystallography and the DFT calculations were performed to determine various structural parameters which were correlated with the X-ray crystal structures. The synthesized compounds were subjected to antimicrobial evaluation and it was found that compounds 5a and 5j were active against gram negative bacterium Escherichia coli whereas compound 5e was active against different fungal strains. Time kill assay was performed to understand the microbial activity of synthesized organoselenium compounds and the toxicity of these compounds was evaluated against human cell lines. Synergistic effects of active compounds 5a and 5e were tested with existing antibiotic drugs which exhibited that the antibiotic combination with synthesized organoselenium compounds efficiently enhanced the antimicrobial activity.
Sanjeev Kumar
Nidhi Sharma
Indresh K. Maurya
Aman K.K. Bhasin
Nishima Wangoo
Paula Brandão
Vítor Félix
K.K. Bhasin
Rohit K. Sharma
2016-10-04T05:30:50Z
2016-10-04T05:44:05Z
http://crdd.osdd.net/open/id/eprint/1914
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1914
2016-10-04T05:30:50Z
Bacteriorhodopsin-ZnO hybrid as a potential sensing element for low-temperature detection of ethanol vapour.
Zinc oxide (ZnO) and bacteriorhodopsin (bR) hybrid nanostructures were fabricated by immobilizing bR on ZnO thin films and ZnO nanorods. The morphological and spectroscopic analysis of the hybrid structures confirmed the ZnO thin film/nanorod growth and functional properties of bR. The photoactivity results of the bR protein further corroborated the sustainability of its charge transport property and biological activity. When exposed to ethanol vapour (reducing gas) at low temperature (70 °C), the fabricated sensing elements showed a significant increase in resistivity, as opposed to the conventional n-type behaviour of bare ZnO nanostructures. This work opens up avenues towards the fabrication of low temperature, photoactivated, nanomaterial-biomolecule hybrid gas sensors.
Saurav Kumar
Sudeshna Bagchi
E.Senthil Prasad
Anupma Sharma
Ritesh Kumar
Rishemjit Kaur
Jagvir Singh
Amol P Bhondekar
2018-03-24T04:16:54Z
2018-03-24T04:16:54Z
http://crdd.osdd.net/open/id/eprint/1973
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1973
2018-03-24T04:16:54Z
Functional and Structural Characterization of Purine Nucleoside Phosphorylase from Kluyveromyces lactis and Its Potential Applications in Reducing Purine Content in Food
Consumption of foods and beverages with high purine content increases the risk of hyperuricemia, which causes gout and can lead to cardiovascular, renal, and other metabolic disorders. As patients often find dietary restrictions challenging, enzymatically lowering purine content in popular foods and beverages offers a safe and attractive strategy to control hyperuricemia. Here, we report structurally and functionally characterized purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP), a key enzyme involved in the purine degradation pathway. We report a 1.97 Å resolution crystal structure of homotrimeric KlacPNP with an intrinsically bound hypoxanthine in the active site. KlacPNP belongs to the nucleoside phosphorylase-I (NP-I) family, and it specifically utilizes 6-oxopurine substrates in the following order: inosine > guanosine > xanthosine, but is inactive towards adenosine. To engineer enzymes with broad substrate specificity, we created two point variants, KlacPNPN256D and KlacPNPN256E, by replacing the catalytically active Asn256 with Asp and Glu, respectively, based on structural and comparative sequence analysis. KlacPNPN256D not only displayed broad substrate specificity by utilizing both 6-oxopurines and 6-aminopurines in the order adenosine > inosine > xanthosine > guanosine, but also displayed reversal of substrate specificity. In contrast, KlacPNPN256E was highly specific to inosine and could not utilize other tested substrates. Beer consumption is associated with increased risk of developing gout, owing to its high purine content. Here, we demonstrate that KlacPNP and KlacPNPN256D could be used to catalyze a key reaction involved in lowering beer purine content. Biochemical properties of these enzymes such as activity across a wide pH range, optimum activity at about 25°C, and stability for months at about 8°C, make them suitable candidates for food and beverage industries. Since KlacPNPN256D has broad substrate specificity, a combination of engineered KlacPNP and other enzymes involved in purine degradation could effectively lower the purine content in foods and beverages.
Gotthard Kunze
Durga Mahor
Anu Priyanka
Gandham S Prasad
Krishan Gopal Thakur
2016-09-29T09:16:55Z
2016-09-29T09:16:55Z
http://crdd.osdd.net/open/id/eprint/1885
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1885
2016-09-29T09:16:55Z
A Novel Triculture System (CC3) for Simultaneous Enzyme Production and Hydrolysis of Common Grasses through Submerged Fermentation.
The perennial grasses are considered as a rich source of lignocellulosic biomass, making it a second generation alternative energy source and can diminish the use of fossil fuels. In this work, four perennial grasses Saccharum arundinaceum, Panicum antidotale, Thysanolaena latifolia, and Neyraudia reynaudiana were selected to verify their potential as a substrate to produce hydrolytic enzymes and to evaluate them as second generation energy biomass. Here, cellulase and hemi-cellulase producing three endophytic bacteria (Burkholderia cepacia BPS-GB3, Alcaligenes faecalis BPS-GB5 and Enterobacter hormaechei BPS-GB8) recovered from N. reynaudiana and S. arundinaceum were selected to develop a triculture (CC3) consortium. During 12 days of submerged cultivation, a 55-70% loss in dry weight was observed and the maximum activity of β-glucosidase (5.36-12.34 IU) and Xylanase (4.33 to 10.91 IU) were observed on 2nd and 6th day respectively, whereas FPase (0.26 to 0.53 IU) and CMCase (2.31 to 4.65 IU) showed maximum activity on 4th day. Around 15-30% more enzyme activity was produced in CC3 as compared to monoculture (CC1) and coculture (CC2) treatments, suggested synergetic interaction among the selected three bacterial strains. Further, the biomass was assessed using Fourier-transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). The FTIR analysis provides important insights into the reduction of cellulose and hemicellulose moieties in CC3 treated biomass and SEM studies shed light into the disruption of surface structure leading to access of cellulose or hemicelluloses microtubules. The hydrolytic potential of the CC3 system was further enhanced due to reduction in lignin as evidenced by 1-4% lignin reduction in biomass compositional analysis. Additionally, laccase gene was detected from A. faecalis and E. hormaechei which further shows the laccase production potential of the isolates. To our knowledge, first time we develop an effective endophytic endogenous bacterial triculture system having potential for the production of extracellular enzymes utilizing S. arundinaceum and N. reynaudiana as lignocellulosic feedstock.
Vincent V Leo
Ajit K Passari
J Beslin Joshi
Vineet K Mishra
Sivakumar Uthandi
N Ramesh
Vijai K Gupta
Ratul Saikia
Vijay C Sonawane
Bhim P Singh
2016-09-29T09:14:12Z
2016-09-29T09:14:12Z
http://crdd.osdd.net/open/id/eprint/1886
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1886
2016-09-29T09:14:12Z
Frienemies of infection: A chronic case of host nuclear receptors acting as cohorts or combatants of infection.
Macrophages and dendritic cells provide critical effector functions to efficiently resist and promptly eliminate infection. Pattern recognition receptors signaling operative in these cell types is imperative for their innate properties. However, it is now emerging that besides these conventional signaling pathways, nuclear receptors coupled gene regulation and transrepression pathways assemble immune regulatory networks. A couple of these networks associated with members of nuclear receptor superfamily decide heterogeneity in macrophages and dendritic cells population and thereby play decisive role in determining protective immunity against bacteria, viruses, fungi, protozoa and helminths. Pathogens also direct shift in the expression of nuclear receptors and their target genes and this is proclaimed to be a sui generis mechanism whereby microbes disconnect the genomic component from the peripheral immune response. Many endogenous and synthetic nuclear receptor ligands have been tested in various in vitro and in vivo infection models to study their effect on pathogen burden. Here, we discuss current advances in our understanding of the composite interactions between nuclear receptor and pathogens and their implications on the causatum infectious diseases.
Sahil Mahajan
Ankita Saini
Rashi Kalra
Pawan Gupta
2016-09-29T09:10:41Z
2016-09-29T09:10:41Z
http://crdd.osdd.net/open/id/eprint/1887
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1887
2016-09-29T09:10:41Z
Amino-Terminal Fusion of Epidermal Growth Factor 4,5,6 Domains of Human Thrombomodulin on Streptokinase Confers Anti-Reocclusion Characteristics along with Plasmin-Mediated Clot Specificity.
Streptokinase (SK) is a potent clot dissolver but lacks fibrin clot specificity as it activates human plasminogen (HPG) into human plasmin (HPN) throughout the system leading to increased risk of bleeding. Another major drawback associated with all thrombolytics, including tissue plasminogen activator, is the generation of transient thrombin and release of clot-bound thrombin that promotes reformation of clots. In order to obtain anti-thrombotic as well as clot-specificity properties in SK, cDNAs encoding the EGF 4,5,6 domains of human thrombomodulin were fused with that of streptokinase, either at its N- or C-termini, and expressed these in Pichia pastoris followed by purification and structural-functional characterization, including plasminogen activation, thrombin inhibition, and Protein C activation characteristics. Interestingly, the N-terminal EGF fusion construct (EGF-SK) showed plasmin-mediated plasminogen activation, whereas the C-terminal (SK-EGF) fusion construct exhibited 'spontaneous' plasminogen activation which is quite similar to SK i.e. direct activation of systemic HPG in absence of free HPN. Since HPN is normally absent in free circulation due to rapid serpin-based inactivation (such as alpha-2-antiplasmin and alpha-2-Macroglobin), but selectively present in clots, a plasmin-dependent mode of HPG activation is expected to lead to a desirable fibrin clot-specific response by the thrombolytic. Both the N- and C-terminal fusion constructs showed strong thrombin inhibition and Protein C activation properties as well, and significantly prevented re-occlusion in a specially designed assay. The EGF-SK construct exhibited fibrin clot dissolution properties with much-lowered levels of fibrinogenolysis, suggesting unmistakable promise in clot dissolver therapy with reduced hemorrhage and re-occlusion risks.
Neeraj Maheshwari
Satish Kantipudi
Anand Maheshwari
Kashika Arora
. Vandana
Neha Kwatra
Girish Sahni
2019-08-03T09:42:07Z
2019-08-03T11:48:49Z
http://crdd.osdd.net/open/id/eprint/2321
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2321
2019-08-03T09:42:07Z
Characterization of enzymes involved in the purine degradation pathway of Kluyveromyces lactis
Durga Mahor
2019-07-20T10:39:58Z
2022-05-26T04:02:48Z
http://crdd.osdd.net/open/id/eprint/2294
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2294
2019-07-20T10:39:58Z
Understanding the role of mammalian glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in iron metabolism
Himanshu Malhotra
2016-09-30T11:36:47Z
2016-09-30T11:36:47Z
http://crdd.osdd.net/open/id/eprint/1913
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1913
2016-09-30T11:36:47Z
Exosomes: Tunable Nano Vehicles for Macromolecular Delivery of Transferrin and Lactoferrin to Specific Intracellular Compartment.
Due to their abundant ubiquitous presence, rapid uptake and increased requirement in neoplastic tissue, the delivery of the iron carrier macromolecules transferrin (Tf) and lactoferrin (Lf) into mammalian cells is the subject of intense interest for delivery of drugs and other target molecules into cells. Utilizing exosomes obtained from cells of diverse origin we confirmed the presence of the multifunctional protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which has recently been characterized as a Tf and Lf receptor. Using a combination of biochemical, biophysical and imaging based methodologies, we demonstrate that GAPDH present in exosomes captures Tf and Lf and subsequently effectively delivers these proteins into mammalian cells. Exosome vesicles prepared had a size of 51.2 ± 23.7 nm. They were found to be stable in suspension with a zeta potential (ζ-potential) of -28.16 ± 1.15 mV. Loading of Tf/Lf did not significantly affect ζ-potential of the exosomes. The carrier protein loaded exosomes were able to enhance the delivery of Tf/Lf by 2 to 3 fold in a diverse panel of cell types. Ninety percent of the internalized cargo via this route was found to be specifically delivered into late endosome and lysosomes. We also found exosomes to be tunable nano vehicles for cargo delivery by varying the amount of GAPDH associated with exosome. The current study opens a new avenue of research for efficient delivery of these vital iron carriers into cells employing exosomes as a nano delivery vehicle.
Himanshu Malhotra
Navdeep Sheokand
Santosh Kumar
Anoop S Chauhan
Manoj Kumar
Priyanka Jakhar
Vishant M Boradia
Chaaya I Raje
Manoj Raje
2016-09-29T09:06:56Z
2016-09-29T09:06:56Z
http://crdd.osdd.net/open/id/eprint/1888
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1888
2016-09-29T09:06:56Z
Eukaryotic-Type Ser/Thr Protein Kinase Mediated Phosphorylation of Mycobacterial Phosphodiesterase Affects its Localization to the Cell Wall.
Phosphodiesterase enzymes, involved in cAMP hydrolysis reaction, are present throughout phylogeny and their phosphorylation mediated regulation remains elusive in prokaryotes. In this context, we focused on this enzyme from Mycobacterium tuberculosis. The gene encoded by Rv0805 was PCR amplified and expressed as a histidine-tagged protein (mPDE) utilizing Escherichia coli based expression system. In kinase assays, upon incubation with mycobacterial Clade I eukaryotic-type Ser/Thr kinases (PknA, PknB, and PknL), Ni-NTA purified mPDE protein exhibited transphosphorylation ability albeit with varying degree. When mPDE was co-expressed one at a time with these kinases in E. coli, it was also recognized by an anti-phosphothreonine antibody, which further indicates its phosphorylating ability. Mass spectrometric analysis identified Thr-309 of mPDE as a phosphosite. In concordance with this observation, anti-phosphothreonine antibody marginally recognized mPDE-T309A mutant protein; however, such alteration did not affect the enzymatic activity. Interestingly, mPDE expressed in Mycobacterium smegmatis yielded a phosphorylated protein that preferentially localized to cell wall. In contrast, mPDE-T309A, the phosphoablative variant of mPDE, did not show such behavior. On the other hand, phosphomimics of mPDE (T309D or T309E), exhibited similar cell wall anchorage as was observed with the wild-type. Thus, our results provide credence to the fact that eukaryotic-type Ser/Thr kinase mediated phosphorylation of mPDE renders negative charge to the protein, promoting its localization on cell wall. Furthermore, multiple sequence alignment revealed that Thr-309 is conserved among mPDE orthologs of M. tuberculosis complex, which presumably emphasizes evolutionary significance of phosphorylation at this residue.
Neha Malhotra
Pradip K Chakraborti
2016-09-29T07:39:05Z
2016-09-29T07:39:05Z
http://crdd.osdd.net/open/id/eprint/1889
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1889
2016-09-29T07:39:05Z
Induction of nodD Gene in a Betarhizobium Isolate, Cupriavidus sp. of Mimosa pudica, by Root Nodule Phenolic Acids.
A range of phenolic acids, viz., p-coumaric acid, 4-hydroxybenzaldehyde, 4-hydroxybenzoic acid, protocatechuic acid, caffeic acid, ferulic acid, and cinnamic acid have been isolated and identified by LC-MS analysis in the roots and root nodules of Mimosa pudica. The effects of identified phenolic acids on the regulation of nodulation (nod) genes have been evaluated in a betarhizobium isolate of M. pudica root nodule. Protocatechuic acid and p-hydroxybenzoic acid were most effective in inducing nod gene, whereas caffeic acid had no significant effect. Phenylalanine ammonia lyase, peroxidase, and polyphenol oxidase activities were estimated, indicating regulation and metabolism of phenolic acids in root nodules. These results showed that nodD gene expression of betarhizobium is regulated by simple phenolic acids such as protocatechuic acid and p-hydroxybenzoic acid present in host root nodule and sustains nodule organogenesis.
Santi M Mandal
Dipjyoti Chakraborty
Suhrid R Dutta
Ananta K Ghosh
Bikas R Pati
Suresh Korpole
Debarati Paul
2018-03-24T04:07:53Z
2018-04-03T04:57:52Z
http://crdd.osdd.net/open/id/eprint/1975
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1975
2018-03-24T04:07:53Z
PEPlife: A Repository of the Half-life of Peptides
Short half-life is one of the key challenges in the field of therapeutic peptides. Various studies have reported enhancement in the stability of peptides using methods like chemical modifications, D-amino acid substitution, cyclization, replacement of labile aminos acids, etc. In order to study this scattered data, there is a pressing need for a repository dedicated to the half-life of peptides. To fill this lacuna, we have developed PEPlife (http://crdd.osdd.net/raghava/peplife), a manually curated resource of experimentally determined half-life of peptides. PEPlife contains 2229 entries covering 1193 unique peptides. Each entry provides detailed information of the peptide, like its name, sequence, half-life, modifications, the experimental assay for determining half-life, biological nature and activity of the peptide. We also maintain SMILES and structures of peptides. We have incorporated web-based modules to offer user-friendly data searching and browsing in the database. PEPlife integrates numerous tools to perform various types of analysis such as BLAST, Smith-Waterman algorithm, GGSEARCH, Jalview and MUSTANG. PEPlife would augment the understanding of different factors that affect the half-life of peptides like modifications, sequence, length, route of delivery of the peptide, etc. We anticipate that PEPlife will be useful for the researchers working in the area of peptide-based therapeutics.
Deepika Mathur
Satya Prakash
Priya Anand
Harpreet Kaur
Piyush Agrawal
Ayesha Mehta
Rajesh Kumar
Sandeep Singh
G.P.S. Raghava
2016-01-29T04:40:43Z
2016-09-29T07:35:48Z
http://crdd.osdd.net/open/id/eprint/1752
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1752
2016-01-29T04:40:43Z
Bacillus cellulasensis sp. nov., isolated from marine sediment.
A novel bacterial strain NIO-1130(T) was isolated from sediment sample taken from Chorao Island, Goa Province, India, and subjected to a taxonomic investigation. The strain was Gram-positive, aerobic, and motile. Phylogenetic analysis based on 16S rRNA gene sequences placed the isolate within the genus Bacillus and strain NIO-1130(T) showed highest sequence similarity with Bacillus halosaccharovorans DSM 25387(T) (98.4 %) and Bacillus niabensis CIP 109816(T) (98.1 %), whereas other Bacillus species showed <97.0 % similarity. Tree based on gyrB gene sequence revealed that strain bacillus group. The major menaquinone was MK-7 and the predominant cellular fatty acids were iso-C15:0, anteiso-C15:0, iso-C17:0, and anteiso-C17:0. The strain showed a DNA G+C content of 39.9 mol%. DNA-DNA hybridization studies revealed that strain NIO-1130(T) exhibits 70 % similarity with Bacillus halosaccharovorans DSM 25387(T) and Bacillus niabensis CIP 109816(T). On the basis of physiological, biochemical, chemotaxonomic and phylogenetic analyses, we consider the isolate to represent a novel species of the genus Bacillus, for which the name Bacillus cellulasensis sp. nov., is proposed. The type strain is NIO-1130(T) (=NCIM 5461(T)=CCTCC AB 2011126(T)).
Rahul Mawlankar
Meghana N Thorat
Srinivasan Krishnamurthi
Syed G Dastager
2019-07-27T09:58:59Z
2019-07-27T11:54:27Z
http://crdd.osdd.net/open/id/eprint/2305
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2305
2019-07-27T09:58:59Z
Evaluation of Caerulomycin A and its analogs for providing relief in secondary iron overload disease in mouse model and Improving Enantioselectivity of a Nitrilase
Pradeep Mishra
2016-09-29T07:32:43Z
2016-09-29T07:32:43Z
http://crdd.osdd.net/open/id/eprint/1890
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1890
2016-09-29T07:32:43Z
Characterization of an Indole-3-Acetamide Hydrolase from Alcaligenes faecalis subsp. parafaecalis and Its Application in Efficient Preparation of Both Enantiomers of Chiral Building Block 2,3-Dihydro-1,4-Benzodioxin-2-Carboxylic Acid.
Both the enantiomers of 2,3-dihydro-1,4-benzodioxin-2-carboxylic acid are valuable chiral synthons for enantiospecific synthesis of therapeutic agents such as (S)-doxazosin mesylate, WB 4101, MKC 242, 2,3-dihydro-2-hydroxymethyl-1,4-benzodioxin, and N-[2,4-oxo-1,3-thiazolidin-3-yl]-2,3-dihydro-1,4-benzodioxin-2-carboxamide. Pharmaceutical applications require these enantiomers in optically pure form. However, currently available methods suffer from one drawback or other, such as low efficiency, uncommon and not so easily accessible chiral resolving agent and less than optimal enantiomeric purity. Our interest in finding a biocatalyst for efficient production of enantiomerically pure 2,3-dihydro-1,4-benzodioxin-2-carboxylic acid lead us to discover an amidase activity from Alcaligenes faecalis subsp. parafaecalis, which was able to kinetically resolve 2,3-dihydro-1,4-benzodioxin-2-carboxyamide with E value of >200. Thus, at about 50% conversion, (R)-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid was produced in >99% e.e. The remaining amide had (S)-configuration and 99% e.e. The amide and acid were easily separated by aqueous (alkaline)-organic two phase extraction method. The same amidase was able to catalyse, albeit at much lower rate the hydrolysis of (S)-amide to (S)-acid without loss of e.e. The amidase activity was identified as indole-3-acetamide hydrolase (IaaH). IaaH is known to catalyse conversion of indole-3-acetamide (IAM) to indole-3-acetic acid (IAA), which is phytohormone of auxin class and is widespread among plants and bacteria that inhabit plant rhizosphere. IaaH exhibited high activity for 2,3-dihydro-1,4-benzodioxin-2-carboxamide, which was about 65% compared to its natural substrate, indole-3-acetamide. The natural substrate for IaaH indole-3-acetamide shared, at least in part a similar bicyclic structure with 2,3-dihydro-1,4-benzodioxin-2-carboxamide, which may account for high activity of enzyme towards this un-natural substrate. To the best of our knowledge this is the first application of IaaH in production of industrially important molecules.
Pradeep Mishra
Suneet Kaur
Amar Nath Sharma
R S Jolly
2016-09-29T07:29:16Z
2016-09-29T07:29:16Z
http://crdd.osdd.net/open/id/eprint/1891
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1891
2016-09-29T07:29:16Z
Reclassification of Bacillus isronensisShivaji et al. 2009 as Solibacillus isronensis comb. nov. and emended description of genus Solibacillus Krishnamurthi et al. 2009.
An investigation into the taxonomic position of Bacillus isronensis MTCC 7902T revealed that the strain shares a common phylogenetic lineage with Solibacillus silvestris MTCC 10789T. It displays considerable overlap in phenotypic properties with the genus Solibacillus, including endospore shape and position, oxidase and catalase activities, presence of iso-C15 : 0, C16 : 1ω7c alcohol and iso-C17 : 1ω7c as major cellular fatty acids, A4α-type cell-wall peptidoglycan, polar lipids and menaquinone pattern. These features reinforce the findings of molecular phylogenetic analyses based on 16S rRNA gene, gyrB gene and 16S-23S internal transcribed spacer (ITS) region sequences and, in line with the recommendations of Kämpfer et al. [Int J Syst Evol Microbiol 56 (2006), 781-786], provide justification for the transfer of Bacillus isronensis from the genus Bacillus to Solibacillus as Solibacillus isronensis comb. nov. The type strain is B3W22T ( = MTCC 7902T = DSM 21046T = JCM 13838T). An emended description of the genus Solibacillus is also provided.
Poonam Mual
Nitin Kumar Singh
Ashish Verma
Peter Schumann
Srinivasan Krishnamurthi
Syed Dastager
Shanmugam Mayilraj
2016-09-06T06:19:35Z
2016-09-06T06:19:35Z
http://crdd.osdd.net/open/id/eprint/1848
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1848
2016-09-06T06:19:35Z
Classify vertebrate hemoglobin proteins by incorporating the evolutionary information into the general PseAAC with the hybrid approach.
Hemoglobin is an oxygen-binding protein widely present in all kingdoms of life from prokaryotic to eukaryotic, but well established in the vertebrate system. An attempt was made to determine the Vertebrate hemoglobin (VerHb) protein on their animal classifications, based on general pseudo amino acid composition (PseAAC)'s evolutionary profiles and hybrid approach. The support vector machine (SVM) has been applied to develop all models, the prediction results further compared according to their animal classification. The performance of the approaches estimated using five-fold cross-validation techniques. The prediction performance was further investigated by receiver operating characteristic (ROC) and prediction score graphs. The prediction accuracy (ACC), sensitivity (SN) and specificity (SP) were examined to find the accurate predictions on the threshold level. Based on the approach, a web-tool has been developed for identifying the VerHb proteins.
S Muthu Krishnan
2016-09-29T07:26:13Z
2018-04-03T05:02:22Z
http://crdd.osdd.net/open/id/eprint/1892
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1892
2016-09-29T07:26:13Z
Novel surface antigen based impedimetric immunosensor for detection of Salmonella typhimurium in water and juice samples.
A specific surface antigen, OmpD has been reported first time as a surface biomarker in the development of selective and sensitive immunosensor for detecting Salmonella typhimurium species. The OmpD surface antigen extraction was done from Salmonella typhimurium serovars, under the optimized growth conditions for its expression. Anti-OmpD antibodies were generated and used as detector probe in immunoassay format on graphene-graphene oxide (G-GO) modified screen printed carbon electrodes. The water samples were spiked with standard Salmonella typhimurium cells, and detection was done by measuring the change in impedimetric response of developed immunosensor to know the concentration of serovar Salmonella typhimurium. The developed immunosensor was able to specifically detect S. typhimurium in spiked water and juice samples with a sensitivity upto 10(1)CFUmL(-1), with high selectivity and very low cross-reactivity with other strains. This is the first report on the detection of Salmonella typhimurum species using a specific biomarker, OmpD. The developed technique could be very useful for the detection of nontyphoidal Salmonellosis and is also important from an epidemiological point of view.
Ruchi Mutreja
Monu Jariyal
Preeti Pathania
Arunima Sharma
Debendra K Sahoo
C Raman Suri
2019-08-03T09:45:19Z
2019-08-03T11:49:46Z
http://crdd.osdd.net/open/id/eprint/2322
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2322
2019-08-03T09:45:19Z
Studies Towards Understanding the Molecular Mechanisms of Amphotericin B Resistance
Anubhav S. Nahar
2016-09-29T07:23:32Z
2016-09-29T07:23:32Z
http://crdd.osdd.net/open/id/eprint/1893
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1893
2016-09-29T07:23:32Z
Biochemical and genome sequence analyses of Megasphaera sp. strain DISK18 from dental plaque of a healthy individual reveals commensal lifestyle.
Much of the work in periodontal microbiology in recent years has focused on identifying and understanding periodontal pathogens. As the majority of oral microbes have not yet been isolated in pure form, it is essential to understand the phenotypic characteristics of microbes to decipher their role in oral environment. In this study, strain DISK18 was isolated from gingival sulcus and identified as a Megasphaera species. Although metagenomics studies revealed Megasphaera species as a major group within the oral habitat, they have never been isolated in cultivable form to date. Therefore, we have characterized the DISK18 strain to better understand its role in the periodontal ecosystem. Strain Megasphaera sp. DISK18 displayed the ability to adhere and self-aggregate, which are essential requisite features for inhabiting and persisting in oral cavity. It also coaggregated with other pioneer oral colonizers like Streptococcus and Lactobacillus species but not with Veillonella. This behaviour points towards its role in the ecologic succession of a multispecies biofilm as an early colonizer. The absence of virulence determining genes as observed in whole genome sequence analysis coupled with an inability to degrade collagen reveals that Megasphaera sp. strain DISK18 is likely not a pathogenic species and emphasizes its commensal lifestyle.
Nayudu Nallabelli
Prashant P Patil
Vijay Kumar Pal
Namrata Singh
Ashish Jain
Prabhu B Patil
Vishakha Grover
Suresh Korpole
2016-09-29T07:21:17Z
2016-10-03T10:14:41Z
http://crdd.osdd.net/open/id/eprint/1894
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1894
2016-09-29T07:21:17Z
ProCarDB: a database of bacterial carotenoids.
Carotenoids have important functions in bacteria, ranging from harvesting light energy to neutralizing oxidants and acting as virulence factors. However, information pertaining to the carotenoids is scattered throughout the literature. Furthermore, information about the genes/proteins involved in the biosynthesis of carotenoids has tremendously increased in the post-genomic era. A web server providing the information about microbial carotenoids in a structured manner is required and will be a valuable resource for the scientific community working with microbial carotenoids.
L N U Nupur
Asheema Vats
Sandeep Kumar Dhanda
G.P.S. Raghava
Anil Kumar Pinnaka
Ashwani Kumar
2018-03-24T03:47:11Z
2018-03-24T03:47:11Z
http://crdd.osdd.net/open/id/eprint/1983
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1983
2018-03-24T03:47:11Z
Infergen Stimulated Macrophages Restrict Mycobacterium tuberculosis Growth by Autophagy and Release of Nitric Oxide
IFN alfacon-1 (Infergen) is a synthetic form of Interferon (IFN)-α2b. Infergen has immunomodulatory activity and is effective against hepatitis C virus. However, the effect of Infergen (IFG) on Mycobacterium tuberculosis (Mtb) has not yet been reported. Therefore, for the first time, we have studied the influence of IFG in constraining the survival of Mtb in human macrophages. We observed that IFG significantly enhanced the maturation and activation of macrophages. Further, it substantially augmented the secretion of IL-6, nitric oxide (NO) and antigen uptake. Moreover, macrophages exhibited remarkably higher bactericidal activity, as evidenced by reduction in the Mtb growth. Infergen-mediated mechanism was different from the type-1 interferons; since it worked through the activation of NF-κB, phosphorylation of STAT-3 and Akt-PI3K that improved the bactericidal activity through autophagy and NO release. In future, IFG immunotherapy can be a novel strategy for treating patients and controlling TB.
Susanta Pahari
Nargis Khan
Mohammad Aqdas
Shikha Negi
Jagdeep Kaur
Javed N. Agrewala
2019-07-27T10:28:26Z
2019-07-27T11:59:08Z
http://crdd.osdd.net/open/id/eprint/2311
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2311
2019-07-27T10:28:26Z
Studies on Metabolic Pathway Engineering based production of Xylitol
Suksham Pal
2019-07-27T10:13:15Z
2019-07-27T11:57:02Z
http://crdd.osdd.net/open/id/eprint/2308
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2308
2019-07-27T10:13:15Z
Studies on Rv3420c encoding a probable N-alpha acetyltransferase and understanding its context in gcp-alr cluster of genes in Mycobacterium tuberculosis
Deepika Pathak
2016-09-29T07:18:45Z
2016-09-29T07:18:45Z
http://crdd.osdd.net/open/id/eprint/1895
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1895
2016-09-29T07:18:45Z
Biochemical evidence for relaxed substrate specificity of Nα-acetyltransferase (Rv3420c/rimI) of Mycobacterium tuberculosis.
Nα-acetylation is a naturally occurring irreversible modification of N-termini of proteins catalyzed by Nα-acetyltransferases (NATs). Although present in all three domains of life, it is little understood in bacteria. The functional grouping of NATs into six types NatA - NatF, in eukaryotes is based on subunit requirements and stringent substrate specificities. Bacterial orthologs are phylogenetically divergent from eukaryotic NATs, and only a couple of them are characterized biochemically. Accordingly, not much is known about their substrate specificities. Rv3420c of Mycobacterium tuberculosis is a NAT ortholog coding for RimI(Mtb). Using in vitro peptide-based enzyme assays and mass-spectrometry methods, we provide evidence that RimI(Mtb) is a protein Nα-acetyltransferase of relaxed substrate specificity mimicking substrate specificities of eukaryotic NatA, NatC and most competently that of NatE. Also, hitherto unknown acetylation of residues namely, Asp, Glu, Tyr and Leu by a bacterial NAT (RimI(Mtb)) is elucidated, in vitro. Based on in vivo acetylation status, in vitro assay results and genetic context, a plausible cellular substrate for RimI(Mtb) is proposed.
Deepika Pathak
Aadil Hussain Bhat
Vandana Sapehia
Jagdish Rai
Alka Rao
2016-09-29T07:16:15Z
2016-09-29T07:16:15Z
http://crdd.osdd.net/open/id/eprint/1896
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1896
2016-09-29T07:16:15Z
Genome Sequence of Type Strains of Genus Stenotrophomonas.
Genomic resource of type strains and historically important strains of genus Stenotrophomonas allowed us to reveal the existence of 18 distinct species by applying modern phylogenomic criterions. Apart from Stenotrophomonas maltophilia, S. africana represents another species of clinical importance. Interestingly, Pseudomonas hibsicola, P. beteli, and S. pavani that are of plant origin are closer to S. maltophilia than the majority of the environmental isolates. The genus has an open pan-genome. By providing the case study on genes encoding metallo-β-lactamase and Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) regions, we have tried to show the importance of this genomic dataset in understanding its ecology.
Prashant P Patil
Samriti Midha
Sanjeet Kumar
Prabhu B Patil
2019-08-03T09:59:47Z
2020-01-04T11:58:38Z
http://crdd.osdd.net/open/id/eprint/2326
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2326
2019-08-03T09:59:47Z
Structural characterization of Sirtuins to aid structure based drug design
Anu Priyanka
2016-09-29T07:13:24Z
2016-09-29T07:13:24Z
http://crdd.osdd.net/open/id/eprint/1897
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1897
2016-09-29T07:13:24Z
Crystal structure of the N-terminal domain of human SIRT7 reveals a three-helical domain architecture.
Human SIRT7 is an NAD(+) dependent deacetylase, which belongs to sirtuin family of proteins. SIRT7, like other sirtuins has conserved catalytic domain and is flanked by N- and C-terminal domains reported to play vital functional roles. Here, we report the crystal structure of the N-terminal domain of human SIRT7 (SIRT7(NTD) ) at 2.3 Å resolution as MBP-SIRT7(NTD) fusion protein. SIRT7(NTD) adopts three-helical domain architecture and comparative structural analyses suggest similarities to some DNA binding motifs and transcription regulators. We also report here the importance of N- and C-terminal domains in soluble expression of SIRT7. Proteins 2016; 84:1558-1563. © 2016 Wiley Periodicals, Inc.
Anu Priyanka
Vipul Solanki
Raman Parkesh
Krishan Gopal Thakur
2018-03-24T03:41:58Z
2018-04-03T07:07:58Z
http://crdd.osdd.net/open/id/eprint/1987
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1987
2018-03-24T03:41:58Z
AVCpred: an integrated web server for prediction and design of antiviral compounds
iral infections constantly jeopardize the global public health due to lack of effective antiviral therapeutics. Therefore, there is an imperative need to speed up the drug discovery process to identify novel and efficient drug candidates. In this study, we have developed quantitative structure–activity relationship (QSAR)‐based models for predicting antiviral compounds (AVCs) against deadly viruses like human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), human herpesvirus (HHV) and 26 others using publicly available experimental data from the ChEMBL bioactivity database. Support vector machine (SVM) models achieved a maximum Pearson correlation coefficient of 0.72, 0.74, 0.66, 0.68, and 0.71 in regression mode and a maximum Matthew's correlation coefficient 0.91, 0.93, 0.70, 0.89, and 0.71, respectively, in classification mode during 10‐fold cross‐validation. Furthermore, similar performance was observed on the independent validation sets. We have integrated these models in the AVCpred web server, freely available at http://crdd.osdd.net/servers/avcpred. In addition, the datasets are provided in a searchable format. We hope this web server will assist researchers in the identification of potential antiviral agents. It would also save time and cost by prioritizing new drugs against viruses before their synthesis and experimental testing.
Abid Qureshi
Gazaldeep Kaur
Manoj Kumar
2016-03-17T09:03:10Z
2016-09-29T07:03:34Z
http://crdd.osdd.net/open/id/eprint/1846
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1846
2016-03-17T09:03:10Z
A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host.
Regardless of the fact that potent drug-regimen is currently available, tuberculosis continues to kill 1.5 million people annually. Tuberculosis patients are not only inflicted by the trauma of disease but they also suffer from the harmful side-effects, immune suppression and drug resistance instigated by prolonged therapy. It is an exigency to introduce radical changes in the existing drug-regime and discover safer and better therapeutic measures. Hence, we designed a novel therapeutic strategy by reinforcing the efficacy of drugs to kill Mtb by concurrently boosting host immunity by L91. L91 is chimera of promiscuous epitope of Acr1 antigen of Mtb and TLR-2 agonist Pam2Cys. The adjunct therapy using drugs and L91 (D-L91) significantly declined the bacterial load in Mtb infected animals. The mechanism involved was through enhancement of IFN-γ(+)TNF-α(+) polyfunctional Th1 cells and IL-17A(+)IFN-γ(+) Th17 cells, enduring memory CD4 T cells and downregulation of PD-1. The down-regulation of PD-1 prevents CD4 T cells from undergoing exhaustion and improves their function against Mtb. Importantly, the immune response observed in animals could be replicated using T cells of tuberculosis patients on drug therapy. In future, D-L91 therapy can invigorate drugs potency to treat tuberculosis patients and reduce the dose and duration of drug-regime.
Pradeep K Rai
Sathi Babu Chodisetti
Sajid Nadeem
Sudeep K Maurya
Uthaman Gowthaman
Weiguang Zeng
Ashok Kumar Janmeja
David C Jackson
J N Agrewala
2016-10-04T06:09:49Z
2016-10-04T06:09:49Z
http://crdd.osdd.net/open/id/eprint/1921
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1921
2016-10-04T06:09:49Z
SigMol: repertoire of quorum sensing signaling molecules in prokaryotes.
Quorum sensing is a widespread phenomenon in prokaryotes that helps them to communicate among themselves and with eukaryotes. It is driven through quorum sensing signaling molecules (QSSMs) in a density dependent manner that assists in numerous biological functions like biofilm formation, virulence factors secretion, swarming motility, bioluminescence, etc. Despite immense implications, dedicated resources of QSSMs are lacking. Therefore, we have developed SigMol (http://bioinfo.imtech.res.in/manojk/sigmol), a specialized repository of these molecules in prokaryotes. SigMol harbors information on QSSMs pertaining to different quorum sensing signaling systems namely acylated homoserine lactones (AHLs), diketopiperazines (DKPs), 4-hydroxy-2-alkylquinolines (HAQs), diffusible signal factors (DSFs), autoinducer-2 (AI-2) and others. Database contains 1382: entries of 182: unique signaling molecules from 215: organisms. It encompasses biological as well as chemical aspects of signaling molecules. Biological information includes genes, preliminary bioassays, identification assays and applications, while chemical detail comprises of IUPAC name, SMILES and structure. We have provided user-friendly browsing and searching facilities for easy data retrieval and comparison. We have gleaned information of diverse QSSMs reported in literature at a single platform 'SigMol'. This comprehensive resource will assist the scientific community in understanding intraspecies, interspecies or interkingdom networking and further help to unfold different facets of quorum sensing and related therapeutics.
Akanksha Rajput
Karambir Kaur
Manoj Kumar
2016-01-29T07:05:07Z
2016-09-29T06:59:21Z
http://crdd.osdd.net/open/id/eprint/1735
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1735
2016-01-29T07:05:07Z
Functional dissection of HAMP domains in NIK1 ortholog from pathogenic yeast Candida lusitaniae.
Nik1 orthologs or group III hybrid histidine kinases (HHK) are ubiquitous signaling molecules in fungal pathogens. Besides osmosensing, they are also involved in hyphal morphogenesis, virulence, and conidiation. They are important molecular targets for antifungal agents. Nik1 orthologs contain a varying number of HAMP domain repeats (poly-HAMP) in the N-terminal region. Poly-HAMP plays a crucial role in their function. So far, the role of HAMP domains in their function has been studied only in a few Nik1 orthologs. In this paper, we describe the functional characterization of a Nik1 ortholog (ClNik1p) from Candida lusitaniae, an emerging and important fungal pathogen. We show that ClNik1p acts as a bona fide osmosensor and negatively regulates the downstream HOG pathway in Saccharomyces cerevisiae. Our data suggests a differential role of the HAMP domains in the functionality of ClNik1p. The HAMP domains H1, H2, H3 and H5 are essential for kinase activity, and H4 domain has a regulatory role. Among the HAMP like linker domains, only H4b was crucial for the activity of ClNik1p.
Anmoldeep Randhawa
Srishti Chawla
Alok K Mondal
2016-09-30T05:45:24Z
2016-09-30T05:45:24Z
http://crdd.osdd.net/open/id/eprint/1834
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1834
2016-09-30T05:45:24Z
Cell-penetrating peptide and antibiotic combination therapy: a potential alternative to combat drug resistance in methicillin-resistant Staphylococcus aureus.
The diverse pattern of resistance by methicillin-resistant Staphylococcus aureus (MRSA) is the major obstacle in the treatment of its infections. The key reason of resistance is the poor membrane permeability of drug molecules. Over the last decade, cell-penetrating peptides (CPPs) have emerged as efficient drug delivery vehicles and have been exploited to improve the intracellular delivery of numerous therapeutic molecules in preclinical studies. Therefore, to overcome the drug resistance, we have investigated for the first time the effects of two CPPs (P3 and P8) in combination with four antibiotics (viz. oxacillin, erythromycin, norfloxacin, and vancomycin) against MRSA strains. We found that both CPPs internalized into the MRSA efficiently at very low concentration (<10 μM) which was non-toxic to bacteria as well as mammalian cells and showed no significant hemolytic activity. However, the combinations of CPPs (≤10 μM) and antibiotics showed high toxicity against MRSA as compared to antibiotics alone. The significant finding is that P3 and P8 could lower the MICs against oxacillin, norfloxacin, and vancomycin to susceptible levels (generally <1 μg/mL) for almost all five clinical isolates. Further, the bacterial cell death was confirmed by scanning electron microscopy as well as propidium iodide uptake assay. Simultaneously, time-kill kinetics revealed the increased uptake of antibiotics. In summary, CPPs assist to restore the effectiveness of antibiotics at much lower concentration, eliminate the antibiotic toxicity, and represent the CPP-antibiotic combination therapy as a potential novel weapon to combat MRSA infections.
Harmandeep Kaur Randhawa
Ankur Gautam
Minakshi Sharma
Rakesh Bhatia
Grish C Varshney
G.P.S. Raghava
Hemraj Nandanwar
2016-09-29T06:57:56Z
2016-09-29T06:57:56Z
http://crdd.osdd.net/open/id/eprint/1899
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1899
2016-09-29T06:57:56Z
Nuclear receptor expression atlas in BMDCs: Nr4a2 restricts immunogenicity of BMDCs and impedes EAE.
The nuclear receptor (NR) superfamily of transcription factors regulates various key aspects of physiological processes; however, their role(s) in immune cells' function are just beginning to unravel. Although few NRs have been shown to be critical for dendritic cell (DC) function, a lack of knowledge about their complete representation in DCs has limited the ability to harness their full potential. Here, we performed a comprehensive NR expression profiling and identified the key members of NR superfamily being expressed in immature, immunogenic, and tolerogenic DCs. Comparative analysis revealed discrete changes in the expression of various NRs among the studied DC subtypes, indicating a likely role in the modulation of DC functionality. Next, we characterized Nr4a2, a member of orphan NR family, and found that it suppresses the activation of bone marrow derived dendritic cells triggered by LPS. Overexpression and knockdown of Nr4a2 demonstrated that Nr4a2 orchestrates the expression of immunoregulatory genes, hence inducing a tolerogenic phenotype in bone marrow derived dendritic cells. Furthermore, we also found that Nr4a2 provides protection from EAE by promoting an increase in Treg cells, while limiting effector T cells. Our findings suggest a previously unidentified role for Nr4a2 as a regulator of DC tolerogenicity and demonstrate its potential as therapeutic target in DC-associated pathophysiologies.
Ankita Saini
Sahil Mahajan
Pawan Gupta
2019-07-20T10:28:08Z
2019-08-09T15:09:07Z
http://crdd.osdd.net/open/id/eprint/2293
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2293
2019-07-20T10:28:08Z
Genome based insights into the origin and evolution of Xanthomonas species and Pathovars
. Samriti
2016-09-29T06:54:23Z
2016-09-29T06:54:23Z
http://crdd.osdd.net/open/id/eprint/1900
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1900
2016-09-29T06:54:23Z
Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals.
Neutralizing monoclonal antibodies are being found to be increasingly useful in viral infections. In hepatitis B infection, antibodies are proven to be useful for passive prophylaxis. The preS1 region (21-47a.a.) of HBV contains the viral hepatocyte-binding domain crucial for its attachment and infection of hepatocytes. Antibodies against this region are neutralizing and are best suited for immune-based neutralization of HBV, especially in view of their not recognizing decoy particles. Anti-preS1 (21-47a.a.) antibodies are present in serum of spontaneously recovered individuals. We generated a phage-displayed scFv library using circulating lymphocytes from these individuals and selected four preS1-peptide specific scFvs with markedly distinct sequences from this library. All the antibodies recognized the blood-derived and recombinant preS1 containing antigens. Each scFv showed a discrete binding signature, interacting with different amino acids within the preS1-peptide region. Ability to prevent binding of the preS1 protein (N-terminus 60a.a.) to HepG2 cells stably expressing hNTCP (HepG2-hNTCP-C4 cells), the HBV receptor on human hepatocytes was taken as a surrogate marker for neutralizing capacity. These antibodies inhibited preS1-hepatocyte interaction individually and even better in combination. Such a combination of potentially neutralizing recombinant antibodies with defined specificities could be used for preventing/managing HBV infections, including those by possible escape mutants.
Anurag Sankhyan
Chandresh Sharma
Durgashree Dutta
Tarang Sharma
Kunzang Chosdol
Takaji Wakita
Koichi Watashi
Amit Awasthi
Subrat K Acharya
Navin Khanna
Ashutosh Tiwari
Subrata Sinha
2016-09-29T06:50:58Z
2016-09-29T06:51:04Z
http://crdd.osdd.net/open/id/eprint/1901
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1901
2016-09-29T06:50:58Z
Biosurfactant/s from Lactobacilli species: Properties, challenges and potential biomedical applications.
Lactic acid bacteria are generally believed to have positive roles in maintaining good health and immune system in humans. A number of Lactobacilli spp. are known to produce important metabolites, among which biosurfactants in particular have shown antimicrobial activity against several pathogens in the intestinal tract and female urogenital tract partly through interfering with biofilm formation and adhesion to the epithelial cells surfaces. Around 46 reports are documented on biosurfactant production from Lactobacillus spp. of which six can be broadly classified as cell free biosurfactant and 40 as cell associated biosurfactants and only approximately 50% of those have reported on the structural composition which, in order of occurrence were mainly proteinaceous, glycolipidic, glycoproteins, or glycolipopeptides in nature. Due to the proteinaceous nature, most biosurfactant produced by strains of Lactobacillus are generally believed to be surlactin type with high potential toward impeding pathogens adherence. Researchers have recently focused on the anti-adhesive and antibiofilm properties of Lactobacilli-derived biosurfactants. This review briefly discusses the significance of Lactobacilli-derived biosurfactants and their potential applications in various fields. In addition, we highlight the exceptional prospects and challenges in fermentation economics of Lactobacillus spp.-derived biosurfactants' production processes.
Surekha K Satpute
Gauri R Kulkarni
Arun G Banpurkar
Ibrahim M Banat
Nishigandha S Mone
Rajendra H Patil
Swaranjit Singh Cameotra
2016-09-29T06:44:59Z
2016-09-29T06:44:59Z
http://crdd.osdd.net/open/id/eprint/1902
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1902
2016-09-29T06:44:59Z
PEGylation of Truncated Streptokinase Leads to Formulation of a Useful Drug with Ameliorated Attributes.
Streptokinase (SK) remains a favored thrombolytic agent in the developing world as compared to the nearly 10-fold more expensive human tissue-plasminogen activator (tPA) for the dissolution of pathological fibrin clots in myocardial infarction. However, unlike the latter, SK induces systemic activation of plasmin which results in a greater risk of hemorrhage. Being of bacterial origin, it elicits generation of unwanted antibody and has a relatively short half-life in vivo that needs to be addressed to make it more efficacious clinically. In order to address these lacunae, in the present study we have incorporated cysteine residues specifically at the N- and C-termini of partially truncated SK and these were then PEGylated successfully. Some of the obtained derivatives displayed enhanced plasmin resistance, longer half-life (upto several hours), improved fibrin clot-specificity and reduced immune-reactivity as compared to the native SK (nSK). This paves the way for devising next-generation SK-based thrombolytic agent/s that besides being fibrin clot-specific are endowed with an improved efficacy by virtue of an extended in vivo half-life.
Pooja Sawhney
Keya Katare
Girish Sahni
2016-03-08T04:42:07Z
2016-03-08T04:42:07Z
http://crdd.osdd.net/open/id/eprint/1843
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1843
2016-03-08T04:42:07Z
BacHbpred: Support Vector Machine Methods for the Prediction of Bacterial Hemoglobin-Like Proteins
The recent upsurge in microbial genome data has revealed that hemoglobin-like (HbL) proteins may be widely distributed among bacteria and that some organisms may carry more than one HbL encoding gene. However, the discovery of HbL proteins has been limited to a small number of bacteria only. This study describes the prediction of HbL proteins and their domain classification using a machine learning approach. Support vector machine (SVM) models were developed for predicting HbL proteins based upon amino acid composition (AC), dipeptide composition (DC), hybrid method (AC + DC), and position specific scoring matrix (PSSM). In addition, we introduce for the first time a new prediction method based on max to min amino acid residue (MM) profiles. The average accuracy, standard deviation (SD), false positive rate (FPR), confusion matrix, and receiver operating characteristic (ROC) were analyzed. We also compared the performance of our proposed models in homology detection databases. The performance of the different approaches was estimated using fivefold cross-validation techniques. Prediction accuracy was further investigated through confusion matrix and ROC curve analysis. All experimental results indicate that the proposed BacHbpred can be a perspective predictor for determination of HbL related proteins. BacHbpred, a web tool, has been developed for HbL prediction.
MuthuKrishnan Selvaraj
Munish Puri
Kanak L. Dikshit
Christophe Lefevre
2016-02-17T11:06:12Z
2016-09-29T06:41:27Z
http://crdd.osdd.net/open/id/eprint/1842
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1842
2016-02-17T11:06:12Z
Lipoprotein LprI of Mycobacterium tuberculosis Acts as a Lysozyme Inhibitor.
Mycobacterium tuberculosis executes numerous defense strategies for the successful establishment of infection under a diverse array of challenges inside the host. One such strategy that has been delineated in this study is the abrogation of lytic activity of lysozyme by a novel glycosylated and surface-localized lipoprotein, LprI, which is exclusively present in M. tuberculosis complex. The lprI gene co-transcribes with the glbN gene (encoding hemoglobin (HbN)) and both are synchronously up-regulated in M. tuberculosis during macrophage infection. Recombinant LprI, expressed in Escherichia coli, exhibited strong binding (Kd ≤ 2 nm) with lysozyme and abrogated its lytic activity completely, thereby conferring protection to fluorescein-labeled Micrococcus lysodeikticus from lysozyme-mediated hydrolysis. Expression of the lprI gene in Mycobacterium smegmatis (8-10-fold) protected its growth from lysozyme inhibition in vitro and enhanced its phagocytosis and survival during intracellular infection of peritoneal and monocyte-derived macrophages, known to secrete lysozyme, and in the presence of exogenously added lysozyme in secondary cell lines where lysozyme levels are low. In contrast, the presence of HbN enhanced phagocytosis and intracellular survival of M. smegmatis only in the absence of lysozyme but not under lysozyme stress. Interestingly, co-expression of the glbN-lprI gene pair elevated the invasion and survival of M. smegmatis 2-3-fold in secondary cell lines in the presence of lysozyme in comparison with isogenic cells expressing these genes individually. Thus, specific advantage against macrophage-generated lysozyme, conferred by the combination of LprI-HbN during invasion of M. tuberculosis, may have vital implications on the pathogenesis of tuberculosis.
Deepti Sethi
Sahil Mahajan
Chaahat Singh
Amrita Lama
Mangesh Dattu Hade
Pawan Gupta
Kanak L Dikshit
2019-07-27T10:04:10Z
2019-07-27T11:55:23Z
http://crdd.osdd.net/open/id/eprint/2306
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2306
2019-07-27T10:04:10Z
Synthesis and Evaluation of Caerulomycin A Analogs for Immunosuppression
Amar Nath Sharma
2016-10-04T05:39:28Z
2016-10-04T05:39:28Z
http://crdd.osdd.net/open/id/eprint/1915
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1915
2016-10-04T05:39:28Z
Photon induced separation of bio-nano hybrid complex based on carbon nanotubes and optically active bacteriorhodopsin
We report optically induced rapid aggregation and subsequent separation of selective single-walled carbon nanotubes (SWNT) functionalized with bacteriorhodopsin. Induced aggregation rate depends on the absorption of bacteriorhodopsin. Optically separated, bio-nano hybrid complexes show stable, preferential binding with SWNTs of specific diameters whereas, unbound SWNTs remains well-dispersed in the solution.
Astha Sharma
E.Senthil Prasad
Harsh Chaturvedi
2019-07-27T10:36:27Z
2019-07-29T09:06:21Z
http://crdd.osdd.net/open/id/eprint/2313
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2313
2019-07-27T10:36:27Z
Understanding Genome Complexity and bacterial social networking in Myxobacteria
Gaurav Sharma
2016-09-29T06:40:09Z
2016-09-29T06:40:09Z
http://crdd.osdd.net/open/id/eprint/1903
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1903
2016-09-29T06:40:09Z
Complete Genome of the Starch-Degrading Myxobacteria Sandaracinus amylolyticus DSM 53668T.
Myxobacteria are members of δ-proteobacteria and are typified by large genomes, well-coordinated social behavior, gliding motility, and starvation-induced fruiting body formation. Here, we report the 10.33 Mb whole genome of a starch-degrading myxobacterium Sandaracinus amylolyticus DSM 53668(T) that encodes 8,962 proteins, 56 tRNA, and two rRNA operons. Phylogenetic analysis, in silico DNA-DNA hybridization and average nucleotide identity reveal its divergence from other myxobacterial species and support its taxonomic characterization into a separate family Sandaracinaceae, within the suborder Sorangiineae. Sequence similarity searches using the Carbohydrate-active enzymes (CAZyme) database help identify the enzyme repertoire of S. amylolyticus involved in starch, agar, chitin, and cellulose degradation. We identified 16 α-amylases and two γ-amylases in the S. amylolyticus genome that likely play a role in starch degradation. While many of the amylases are seen conserved in other δ-proteobacteria, we notice several novel amylases acquired via horizontal transfer from members belonging to phylum Deinococcus-Thermus, Acidobacteria, and Cyanobacteria. No agar degrading enzyme(s) were identified in the S. amylolyticus genome. Interestingly, several putative β-glucosidases and endoglucanases proteins involved in cellulose degradation were identified. However, the absence of cellobiohydrolases/exoglucanases corroborates with the lack of cellulose degradation by this bacteria.
Gaurav Sharma
Indu Khatri
Srikrishna Subramanian
2016-09-29T06:34:40Z
2016-09-29T06:34:40Z
http://crdd.osdd.net/open/id/eprint/1904
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1904
2016-09-29T06:34:40Z
Complete Genome Sequence and Comparative Genomics of a Novel Myxobacterium Myxococcus hansupus.
Myxobacteria, a group of Gram-negative aerobes, belong to the class δ-proteobacteria and order Myxococcales. Unlike anaerobic δ-proteobacteria, they exhibit several unusual physiogenomic properties like gliding motility, desiccation-resistant myxospores and large genomes with high coding density. Here we report a 9.5 Mbp complete genome of Myxococcus hansupus that encodes 7,753 proteins. Phylogenomic and genome-genome distance based analysis suggest that Myxococcus hansupus is a novel member of the genus Myxococcus. Comparative genome analysis with other members of the genus Myxococcus was performed to explore their genome diversity. The variation in number of unique proteins observed across different species is suggestive of diversity at the genus level while the overrepresentation of several Pfam families indicates the extent and mode of genome expansion as compared to non-Myxococcales δ-proteobacteria.
Gaurav Sharma
Tarun Narwani
Srikrishna Subramanian
2016-09-30T05:41:03Z
2016-09-30T05:41:03Z
http://crdd.osdd.net/open/id/eprint/1837
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1837
2016-09-30T05:41:03Z
Pentoxifylline triggers autophagy via ER stress response that interferes with Pentoxifylline induced apoptosis in human melanoma cells.
Pentoxifylline (PTX), a non-specific phosphodiesterase inhibitor is known to inhibit the growth of various cancer cells including melanoma. Here in this study, we have found that PTX induces autophagy in human melanoma cell lines (A375 and MeWo). Induction of autophagy is associated with the increase in Atg5 expression as knockdown of Atg5 effectively inhibited PTX mediated autophagy. A decrease in mTOR activation was also observed after PTX treatment. We observed that autophagy was activated as a downstream effector mechanism of ER stress induced by PTX. ER stress response was confirmed by upregulation of IRE-1α, GRP78 and CHOP expression. PTX treatment also resulted in an increase in intracellular calcium (Ca(2+)) level. Ca(2+) is the central player as blocking Ca(2+) by intracellular calcium chelator (BAPTA-AM) effectively inhibited the PTX induced ER stress response as well as autophagy. Moreover, silencing of CHOP also resulted in autophagy inhibition with a decrease in Atg5 expression. Collectively, PTX triggers ER stress response followed by induction of autophagy via involvement of Ca(2+)→CHOP→Atg5 signalling cascade. Interestingly, inhibition of intracellular calcium level by BAPTA-AM significantly increased PTX mediated cell death by augmenting intrinsic apoptotic pathway. Inhibition of autophagy by the ATG5 siRNA and pharmacological inhibitor, chloroquine also enhances PTX induced cell death. Taken together, our results clearly indicate that activation of ER stress response and autophagy provides resistance to PTX mediated apoptosis, and thus, interferes with the anticancer activity of PTX in human melanoma cells.
Kapil Sharma
Mohammad Ishaq
Gaurav Sharma
Mohammad Aslam Khan
Rajesh Kumar Dutta
Sekhar Majumdar
2016-09-29T06:31:41Z
2016-09-29T06:31:41Z
http://crdd.osdd.net/open/id/eprint/1905
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1905
2016-09-29T06:31:41Z
Characterization of heat induced spherulites of lysozyme reveals new insight on amyloid initiation.
Here, we report results obtained during our experiments to visualize how heat transforms globular protein, lysozyme into building block of β-amyloids. Light scattering experiments showed formation of lower order associated species around 50-70 °C followed by rapid cooperativity to β-amyloid fibrils. Interestingly, crystallization drops set at higher temperatures either led to aggregates or spherulites. The latter possess an amorphous β-fibril rich core with thin crystalline needles projecting outwards. Diffraction of the crystalline outgrowths revealed novel dimers and trimers of lysozyme where individual chains were similar to monomer with marginal gain in β-sheet content. Importantly, analysis of Amide I stretching frequencies showed that protein loses its secondary structure at temperatures higher than where we obtained crystals followed by rapid gain in β-sheet content. Interestingly, attempts to use the needles as seeds for more crystals led to "broom-like" fibril formations at the ends. Further, aggregation inhibitors like arginine and benzyl alcohol completely obliterated spherulites formation during crystallization. Refinement of crystals of lysozyme in presence of these molecules showed these small molecules bind to the interfaces of heat associated dimers and trimers. Overall our work concludes that heat induced weakly associated structures of lysozyme are the first step towards its amyloid formation.
Pankaj Sharma
Neha Verma
Pradip Kumar Singh
Suresh Korpole
. Ashish
2019-07-27T10:31:34Z
2019-07-27T12:00:10Z
http://crdd.osdd.net/open/id/eprint/2312
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2312
2019-07-27T10:31:34Z
Investigation of ligand binding by X-type lectins and Ranaspumin-4
Shailza Sharma
2019-07-27T09:39:45Z
2019-07-27T11:48:17Z
http://crdd.osdd.net/open/id/eprint/2301
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2301
2019-07-27T09:39:45Z
An attempt to explore the therapeutic potential of Pentoxifylline against melanoma skin cancer
Kapil Sharma
2016-09-29T06:28:36Z
2016-09-29T06:28:36Z
http://crdd.osdd.net/open/id/eprint/1841
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1841
2016-09-29T06:28:36Z
Reverse overshot water-wheel retroendocytosis of Apo Transferrin extrudes cellular iron.
Iron a vital micronutrient for all organisms must be managed judiciously as both, deficiency or excess can trigger severe pathology. While cellular iron import is well understood its export is thought to be limited to transmembrane extrusion via ferroportin the only known mammalian iron exporter. Utilizing primary cells and cell lines (including those with no discernible expression of ferroportin on their surface) we demonstrate that upon iron loading the multifunctional enzyme Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that is recruited to the cell surface treadmills apo transferrin (apo Tf) in and out of the cell. Kinetic analysis utilizing; labeled ligand, GAPDH knock down cells, Fe(55) labeled cells and pharmacological inhibitors of endocytosis confirmed GAPDH dependent apo Tf internalization as a prerequisite for cellular iron export. These studies define an unusual rapid recycling process of retroendocytosis for cellular iron extrusion, a process mirroring receptor mediated internalization that has never before been considered for maintenance of cellular cationic homeostasis. Modulation of this unusual pathway could provide insights for management of iron overload disorders.
Navdeep Sheokand
Himanshu Malhotra
Anoop Singh Chauhan
Manoj Kumar
Surbhi Chaudhary
Anil Patidar
Vishant Mahendra Boradia
Chaaya Iyengar Raje
Manoj Raje
2018-03-24T04:04:08Z
2018-03-24T04:04:08Z
http://crdd.osdd.net/open/id/eprint/1978
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1978
2018-03-24T04:04:08Z
Occurrence of Diverse Antimicrobial Resistance Determinants in Genetically Unrelated Biocide Tolerant Klebsiella pneumoniae
Nosocomial infections due to Klebsiella pneumoniae is a significant problem in health care settings worldwide. In this study, we examined the antimicrobial susceptibility, genetic profiles and mechanisms of antibiotic resistance in K. pneumoniae isolates of Indian origin. To our knowledge this is the first report demonstrating the high prevalence of β-lactamases, aminoglycoside modifying enzymes, quinolone resistance genes besides demonstrating the involvement of active efflux in K. pneumoniae Indian isolates. This study has enabled us to correlate the phenotypic and genotypic characteristics in K. pneumoniae, providing an important base for continued monitoring and epidemiological studies of this emerging nosocomial pathogen in Indian hospitals.
Deepak Shukla
Amitabha Mondal
Manjunath Venkataramaiah
Govindan Rajamohan
Vijaya Bharathi Srinivasan
2016-09-29T06:20:45Z
2016-09-29T06:20:45Z
http://crdd.osdd.net/open/id/eprint/1836
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1836
2016-09-29T06:20:45Z
BLAST-based structural annotation of protein residues using Protein Data Bank.
In the era of next-generation sequencing where thousands of genomes have been already sequenced; size of protein databases is growing with exponential rate. Structural annotation of these proteins is one of the biggest challenges for the computational biologist. Although, it is easy to perform BLAST search against Protein Data Bank (PDB) but it is difficult for a biologist to annotate protein residues from BLAST search.
Harinder Singh
G.P.S. Raghava
2016-09-29T06:23:42Z
2016-09-29T06:23:42Z
http://crdd.osdd.net/open/id/eprint/1906
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1906
2016-09-29T06:23:42Z
A web server for analysis, comparison and prediction of protein ligand binding sites.
One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands.
Harinder Singh
Hemant Kumar Srivastava
G.P.S. Raghava
2019-07-20T09:59:35Z
2019-07-20T11:49:43Z
http://crdd.osdd.net/open/id/eprint/2287
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2287
2019-07-20T09:59:35Z
Functional Characterization of Dimerization Domain variants of HapR and its Homologues
Richa Singh
2019-07-27T09:17:59Z
2019-07-27T11:43:34Z
http://crdd.osdd.net/open/id/eprint/2297
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2297
2019-07-27T09:17:59Z
Computer aided structural annotation of peptides with emphasis on therapeutic peptides
Sandeep Singh
2016-01-29T06:45:38Z
2016-09-29T06:14:42Z
http://crdd.osdd.net/open/id/eprint/1742
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1742
2016-01-29T06:45:38Z
SATPdb: a database of structurally annotated therapeutic peptides.
SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics.
Sandeep Singh
Kumardeep Chaudhary
Sandeep Kumar Dhanda
Sherry Bhalla
Salman Sadullah Usmani
Ankur Gautam
Abhishek Tuknait
Piyush Agrawal
Deepika Mathur
G.P.S. Raghava
2016-10-04T06:20:40Z
2016-10-04T06:20:40Z
http://crdd.osdd.net/open/id/eprint/1918
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1918
2016-10-04T06:20:40Z
MSLVP: prediction of multiple subcellular localization of viral proteins using a support vector machine.
Knowledge of the subcellular location (SCL) of viral proteins in the host cell is important for understanding their function in depth. Therefore, we have developed "MSLVP", a two-tier prediction algorithm for predicting multiple SCLs of viral proteins. For this study, data sets of comprehensive viral proteins with experimentally validated SCL annotation were collected from UniProt. Non-redundant (90%) data sets of 3480 viral proteins that belonged to single (2715), double (391) and multiple (374) sites were employed. Additionally, 1687 (30% sequence identity) viral proteins were categorised into single (1366), double (167) and multiple (154) sites. Single, double and multiple locations further comprised of eight, four and six categories, respectively. Viral protein locations include the nucleus, cytoplasm, endoplasmic reticulum, extracellular, single-pass membrane, multi-pass membrane, capsid, remaining others and combinations thereof. Support vector machine based models were developed using sequence features like amino acid composition, dipeptide composition, physicochemical properties and their hybrids. We have employed "one-versus-one" as well as "one-versus-other" strategies for multiclass classification. The performance of "one-versus-one" is better than the "one-versus-other" approach during 10-fold cross-validation. For the 90% data set, we achieved an accuracy, a Matthew's correlation coefficient (MCC) and a receiver operating characteristic (ROC) of 99.99%, 1.00, 1.00; 100.00%, 1.00, 1.00 and 99.90%; 1.00, 1.00 for single, double and multiple locations, respectively. Similar results were achieved for a 30% sequence identity data set. Predictive models for each SCL performed equally well on the independent dataset. The MSLVP web server () can predict subcellular locations i.e. single (8; including single and multi-pass membrane), double (4) and multiple (6). This would be helpful for elucidating the functional annotation of viral proteins and potential drug targets.
Anamika Thakur
Akanksha Rajput
Manoj Kumar
2016-09-29T06:12:59Z
2016-09-29T06:12:59Z
http://crdd.osdd.net/open/id/eprint/1907
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1907
2016-09-29T06:12:59Z
Structural and functional insights into an archaeal L-asparaginase obtained through the linker-less assembly of constituent domains. Corrigendum.
A correction is made to Fig. 7 in the article by Tomar et al. [(2014). Acta Cryst. D70, 3187-3197].
Rachana Tomar
Pankaj Sharma
Ankit Srivastava
Saurabh Bansal
Bishwajit Kundu
. Ashish
2019-07-27T10:40:16Z
2019-07-29T09:04:47Z
http://crdd.osdd.net/open/id/eprint/2314
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/2314
2019-07-27T10:40:16Z
Exploring the phenomenon of biofilm formation in Mycobacterium tuberculosis
Abhishek Trivedi
2016-09-29T06:05:27Z
2018-10-31T06:13:01Z
http://crdd.osdd.net/open/id/eprint/1908
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1908
2016-09-29T06:05:27Z
Thiol reductive stress induces cellulose-anchored biofilm formation in Mycobacterium tuberculosis.
Mycobacterium tuberculosis (Mtb) forms biofilms harbouring antibiotic-tolerant bacilli in vitro, but the factors that induce biofilm formation and the nature of the extracellular material that holds the cells together are poorly understood. Here we show that intracellular thiol reductive stress (TRS) induces formation of Mtb biofilms in vitro, which harbour drug-tolerant but metabolically active bacteria with unchanged levels of ATP/ADP, NAD(+)/NADH and NADP(+)/NADPH. The development of these biofilms requires DNA, RNA and protein synthesis. Transcriptional analysis suggests that Mtb modulates only ∼7% of its genes for survival in biofilms. In addition to proteins, lipids and DNA, the extracellular material in these biofilms is primarily composed of polysaccharides, with cellulose being a key component. Our results contribute to a better understanding of the mechanisms underlying Mtb biofilm formation, although the clinical relevance of Mtb biofilms in human tuberculosis remains unclear.
Abhishek Trivedi
Parminder Singh Mavi
Deepak Bhatt
Ashwani Kumar
2016-09-29T06:00:35Z
2016-09-29T06:00:35Z
http://crdd.osdd.net/open/id/eprint/1909
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1909
2016-09-29T06:00:35Z
A label-free electrochemical immunosensor for the detection of cardiac marker using graphene quantum dots (GQDs).
A label-free immunosensor based on electrochemical impedance spectroscopy has been developed for the sensitive detection of a cardiac biomarker myoglobin (cMyo). Hydrothermally synthesized graphene quantum dots (GQDs) have been used as an immobilized template on screen printed electrodes for the construction of an impedimetric sensor platform. The GQDs-modified electrode was conjugated with highly specific anti-myoglobin antibodies to develop the desired immunosensor. The values of charge transfer resistance (Rct) were monitored as a function of varying antigen concentration. The Rct value of the immunosensor showed a linear increase (from 0.20 to 0.31kΩ) in the range of 0.01-100ng/mL cMyo. The specific detection of cMyo was also made in the presence of other competing proteins. The limit of detection for the proposed immunosensor was estimated as 0.01ng/mL which is comparable to the standard ELISA techniques.
Satish K Tuteja
Rui Chen
Manil Kukkar
Chung Kil Song
Ruchi Mutreja
Suman Singh
Ashok K Paul
Haiwon Lee
Ki-Hyun Kim
Akash Deep
C Raman Suri
2016-09-29T05:56:58Z
2016-09-29T05:56:58Z
http://crdd.osdd.net/open/id/eprint/1910
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1910
2016-09-29T05:56:58Z
Mechanism of increased clearance of glycated albumin by proximal tubule cells.
Serum albumin is the most abundant plasma protein and has a long half-life due to neonatal Fc receptor (FcRn)-mediated transcytosis by many cell types, including proximal tubule cells of the kidney. Albumin also interacts with, and is modified by, many small and large molecules. Therefore, the focus of the present study was to address the impact of specific known biological albumin modifications on albumin-FcRn binding and cellular handling. Binding at pH 6.0 and 7.4 was performed since FcRn binds albumin strongly at acidic pH and releases it after transcytosis at physiological pH. Equilibrium dissociation constants were measured using microscale thermophoresis. Since studies have shown that glycated albumin is excreted in the urine at a higher rate than unmodified albumin, we studied glucose and methylgloxal modified albumins (21 days). All had reduced affinity to FcRn at pH 6.0, suggesting these albumins would not be returned to the circulation via the transcytotic pathway. To address why modified albumin has reduced affinity, we analyzed the structure of the modified albumins using small-angle X-ray scattering. This analysis showed significant structural changes occurring to albumin with glycation, particularly in the FcRn-binding region, which could explain the reduced affinity to FcRn. These results offer an explanation for enhanced proximal tubule-mediated sorting and clearance of abnormal albumins.
Mark C Wagner
Jered Myslinski
Shiv Pratap
Brittany Flores
George Rhodes
Silvia B Campos-Bilderback
Ruben M Sandoval
Sudhanshu Kumar
Monika Patel
. Ashish
Bruce A Molitoris
2016-09-29T05:49:15Z
2016-09-29T05:50:37Z
http://crdd.osdd.net/open/id/eprint/1911
This item is in the repository with the URL: http://crdd.osdd.net/open/id/eprint/1911
2016-09-29T05:49:15Z
Phosphorylation Modulates Catalytic Activity of Mycobacterial Sirtuins.
Sirtuins are NAD(+)-dependent deacetylases involved in the regulation of diverse cellular processes and are conserved throughout phylogeny. Here we report about in vitro transphosphorylation of the only NAD(+)-dependent deacetylase (mDAC) present in the genome of Mycobacterium tuberculosis by eukaryotic-type Ser/Thr kinases, particularly PknA. The phosphorylated mDAC displayed decreased deacetylase activity compared to its unphosphorylated counterpart. Mass-spectrometric study identified seven phosphosites in mDAC; however, mutational analysis highlighted major contribution of Thr-214 for phosphorylation of the protein. In concordance to this observation, variants of mDAC substituting Thr-214 with either Ala (phospho-ablated) or Glu (phosphomimic) exhibited significantly reduced deacetylase activity suggesting phosphorylation mediated control of enzymatic activity. To assess the role of phosphorylation towards functionality of mDAC, we opted for a sirtuin knock-out strain of Escherichia coli (Δdac), where interference of endogenous mycobacterial kinases could be excluded. The Δdac strain in nutrient deprived acetate medium exhibited compromised growth and complementation with mDAC reversed this phenotype. The phospho-ablated or phosphomimic variant, on the other hand, was unable to restore the functionality of mDAC indicating the role of phosphorylation per se in the process. We further over-expressed mDAC or mDAC-T214A as His-tagged protein in M. smegmatis, where endogenous eukaryotic-type Ser/Thr kinases are present. Anti-phosphothreonine antibody recognized both mDAC and mDAC-T214A proteins in western blotting. However, the extent of phosphorylation as adjudged by scanning the band intensity, was significantly low in the mutant protein (mDAC-T214A) compared to that of the wild-type (mDAC). Furthermore, expression of PknA in the mDAC complemented Δdac strain was able to phosphorylate M. tuberculosis sirtuin. The growth profile of this culture in acetate medium was slow compared to that transformed with only vector. On the other hand, use of a kinase dead variant, PknA-K42N instead of PknA, did not display such behavior, which again supported phosphorylation mediated control of mDAC protein. Thus, our results ostensibly render evidence for cross-talk between two distinct post-translational modifications, phosphorylation and deacetylation, in any bacteria. Bioinformatic analysis further indicated conservation of Thr-214 among different mDAC orthologs, thereby arguing the event as mycobacteria specific.
Ghanshyam S Yadav
Sandeep K Ravala
Neha Malhotra
Pradip K Chakraborti