creators_name: Jangra, Manoj
creators_name: Randhawa, Harmandeep Kaur
creators_name: Kaur, Manpreet
creators_name: Srivastava, Anugya
creators_name: Maurya, Navdezda
creators_name: Patil, Prashant P
creators_name: Jaswal, Pallavi
creators_name: Arora, Ashish
creators_name: Patil, Prabhu B
creators_name: Raje, Manoj
creators_name: Nandanwar, Hemraj
type: article
datestamp: 2019-03-19 15:05:07
lastmod: 2019-03-19 15:05:07
metadata_visibility: show
title: Purification, Characterization and  Evaluation of Polymyxin A From : An Underexplored Member of the Polymyxin Family.
ispublished: pub
subjects: QR
keywords: Paenibacillus dendritiformis; antibiotic-resistance; antimicrobial agent; gram-negative infections; polymyxin A
abstract: Nosocomial infections caused by antibiotic-resistant Gram-negative pathogens are of grave concern today. Polymyxins are considered as the last resorts of therapy to treat these multi-drug resistant (MDR) bacteria. But their associated nephrotoxicity and neurotoxicity calls for the development of safer polymyxin therapy until novel and less toxic antibiotics are discovered. No other polymyxin molecule except polymyxin B and E (colistin) is explored thoroughly in literature to demonstrate its clinical relevance. In the present study, we have isolated two antimicrobial compounds named P1 and P2 from the soil isolate  strain PV3-16, which we later identified as polymyxin A and A respectively. We tested their minimum inhibitory concentrations (MICs) against MDR clinical isolates, performed membrane permeabilization assays and determined their interaction with lipopolysaccharide (LPS). Finally, we studied their toxicity against human Leukemic monocyte cell line (THP-1) and embryonic kidney cell line (HEK 293). Both compounds displayed equal efficacy when compared with standard polymyxins. P1 was 2-4 fold more active in most of the clinical strains tested. Moreover, P1 showed higher affinity toward LPS. In cytotoxicity studies, P1 had IC value (>1000 μg/ml) similar to colistin against HEK cells but immune cells, i.e., THP-1 cell lines were more sensitive to polymyxins. P1 showed less toxicity in THP-1 cell line than all other polymyxins checked. To sum up, P1 (polymyxin A) possessed better efficacy than polymyxin B and E and had least toxicity to immune cells. Since polymyxin A was not investigated thoroughly, we performed the comprehensive  assessment of this molecule. Moreover, this is the first report of isolation and characterization of polymyxin A from . This compound should be further investigated for its  efficacy and toxicity to develop it as a drug candidate.
date: 2018-11-23
date_type: published
publication: Frontiers in microbiology
volume: 9
publisher: Frontiers Media S.A
pagerange: 2864
refereed: TRUE
issn: 1664-302X
official_url: https://www.frontiersin.org/articles/10.3389/fmicb.2018.02864/full
citation:   Jangra, Manoj and Randhawa, Harmandeep Kaur and Kaur, Manpreet and Srivastava, Anugya and Maurya, Navdezda and Patil, Prashant P and Jaswal, Pallavi and Arora, Ashish and Patil, Prabhu B and Raje, Manoj and Nandanwar, Hemraj  (2018) Purification, Characterization and Evaluation of Polymyxin A From : An Underexplored Member of the Polymyxin Family.  Frontiers in microbiology, 9.  p. 2864.  ISSN 1664-302X