@prefix epid: .
@prefix dc: .
@prefix geo: .
@prefix bibo: .
@prefix owl: .
@prefix void: .
@prefix event: .
@prefix skos: .
@prefix xsd: .
@prefix cc: .
@prefix ep: .
@prefix foaf: .
@prefix rdf: .
@prefix rdfs: .
@prefix eprel: .
@prefix dct: .
<>
foaf:primaryTopic ;
rdfs:comment "The repository administrator has not yet configured an RDF license."^^xsd:string .
dc:format "text/html";
dc:title "HTML Summary of #3476 \n\nTargeting Mycobacterium tuberculosis GAPDH elicits potent bactericidal responses by dysregulating enzyme activity, redox dynamics and iron acquisition\n\n";
foaf:primaryTopic .
rdf:_1 ;
rdf:_2 ;
rdf:_3 ;
rdf:_4 ;
rdf:_5 ;
rdf:_6 ;
rdf:_7 ;
rdf:_8 ;
rdf:_9 ;
rdf:_10 ;
rdf:_11 ;
rdf:_12 ;
rdf:_13 ;
rdf:_14 ;
rdf:_15 ;
rdf:_16 ;
rdf:_17 ;
rdf:_18 .
bibo:abstract "Mycobacterium tuberculosis (Mtb) Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is indispensable for glycolysis, it also performs several critical non-metabolic functions. In the present study, we demonstrate that CRISPRi silencing of GAPDH inhibited enzyme activity and iron acquisition via human transferrin (Tf)/lactoferrin (Lf). GAPDH silencing also enhanced reactive oxygen species (ROS) and ROS induced damage suggesting its role as a redox sensor. We then examined the impact of GAPDH inhibition in Mtb using small molecule inhibitors. Vitamin C (VC) was selected considering its potent bactericidal effects against Mtb and its inhibition of human GAPDH resulting in its efficacy against cancer cells. The GAPDH inhibitors Ethyl bromopyruvate (EBP) and Koningic acid (KA) are anti-cancer agents that target the glycolytic activity of GAPDH. In contrast, TCH346 was identified as a neuroprotective agent, wherein it targets the non-metabolic function of GAPDH induced apoptotic signalling. The effects of inhibitors, alone or in combination with VC mirrored the cellular effects of GAPDH silencing, resulting in significant anti-bacterial activity. VC induced iron mobilization which coupled with GAPDH inhibitors induced a veritable ``double whammy'' resulting in massive increase in ROS and downstream effects. The efficacy of these treatments was assessed in a murine model, confirming that VC augmented the potent anti-tubercular activity induced by EBP and TCH346. Overall, this study identifies the crucial function of Mtb GAPDH as a redox sensor and highlights the potential of targeting its pleiotropic cellular functions towards drug discovery. In addition, the efficacy of TCH346 provides an opportunity of drug-repurposing as a strategy for therapy."^^xsd:string;
bibo:authorList ;
bibo:status ,
;
bibo:volume "247";
dct:creator ,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
;
dct:date "2026-04";
dct:isPartOf ,
;
dct:publisher ;
dct:subject ;
dct:title "Targeting Mycobacterium tuberculosis GAPDH elicits potent bactericidal responses by dysregulating enzyme activity, redox dynamics and iron acquisition"^^xsd:string;
rdf:type bibo:AcademicArticle,
bibo:Article,
ep:ArticleEPrint,
ep:EPrint;
rdfs:seeAlso .
rdf:type skos:Concept;
skos:prefLabel "QR Microbiology"@en .
foaf:name "ELSEVIER SCIENCE INC"^^xsd:string;
rdf:type foaf:Organization .
foaf:familyName "Yadav"^^xsd:string;
foaf:givenName "Vinay Kumar"^^xsd:string;
foaf:name "Vinay Kumar Yadav"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Sravani"^^xsd:string;
foaf:givenName "Gattadi"^^xsd:string;
foaf:name "Gattadi Sravani"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Sindhu"^^xsd:string;
foaf:givenName "Anurag"^^xsd:string;
foaf:name "Anurag Sindhu"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Imran"^^xsd:string;
foaf:givenName "Mohmmad"^^xsd:string;
foaf:name "Mohmmad Imran"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Kumari"^^xsd:string;
foaf:givenName "Anjali"^^xsd:string;
foaf:name "Anjali Kumari"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Chopra"^^xsd:string;
foaf:givenName "Sidharth"^^xsd:string;
foaf:name "Sidharth Chopra"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Agarwal"^^xsd:string;
foaf:givenName "Nisheeth"^^xsd:string;
foaf:name "Nisheeth Agarwal"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Malik"^^xsd:string;
foaf:givenName "Pradip"^^xsd:string;
foaf:name "Pradip Malik"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Raje"^^xsd:string;
foaf:givenName "Manoj"^^xsd:string;
foaf:name "Manoj Raje"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Dhiman"^^xsd:string;
foaf:givenName "Asmita"^^xsd:string;
foaf:name "Asmita Dhiman"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Priya"^^xsd:string;
foaf:givenName "Gaddam Laxmi"^^xsd:string;
foaf:name "Gaddam Laxmi Priya"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Garg"^^xsd:string;
foaf:givenName "Prabha"^^xsd:string;
foaf:name "Prabha Garg"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Ahmad"^^xsd:string;
foaf:givenName "Mohammad Naiyaz"^^xsd:string;
foaf:name "Mohammad Naiyaz Ahmad"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Gani"^^xsd:string;
foaf:givenName "Zahid"^^xsd:string;
foaf:name "Zahid Gani"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Raje"^^xsd:string;
foaf:givenName "Chaaya Iyengar"^^xsd:string;
foaf:name "Chaaya Iyengar Raje"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Dasgupta"^^xsd:string;
foaf:givenName "Arunava"^^xsd:string;
foaf:name "Arunava Dasgupta"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Kumar"^^xsd:string;
foaf:givenName "Ajay"^^xsd:string;
foaf:name "Ajay Kumar"^^xsd:string;
rdf:type foaf:Person .
foaf:familyName "Kumar"^^xsd:string;
foaf:givenName "Rajender"^^xsd:string;
foaf:name "Rajender Kumar"^^xsd:string;
rdf:type foaf:Person .
foaf:name "FREE RADICAL BIOLOGY AND MEDICINE"^^xsd:string;
rdf:type bibo:Collection .