title: Rv3080c regulates the rate of inhibition of mycobacteria by isoniazid through FabD.
abstract: The mycobacterial FASII multi-enzyme complex has been identified to be a target of Ser/Thr protein kinases (STPKs) of Mycobacterium tuberculosis (MTB), with substrates, including the malonyl-CoA:ACP transacylase (FabD) and the β-ketoacyl-ACP synthases KasA and KasB. These proteins are phosphorylated by various kinases in vitro. The present study links the correlation of FASII pathway with serine threonine protein kinase of MTB. In the preliminary finding, we have shown that mycobacterial protein Rv3080c (PknK) phosphorylates FabD and the knockdown of PknK protein in mycobacteria down regulates FabD expression. This event leads to the differential inhibition of mycobacteria in the presence of isoniazid (INH), as the inhibition of growth of mycobacteria in the presence of INH is enhanced in PknK deficient mycobacteria.
authors.affiliation: Department of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226001, India.
authors.forename: Ruma
authors.initials: R
authors.lastname: Kumari
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.forename: Sameer
authors.initials: S
authors.lastname: Tiwari
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Tripathi
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Srivastava
mesh_terms: D051080:Acyl-Carrier Protein S-Malonyltransferase / Q000378:metabolism*; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000378:metabolism*; D054889:Fatty Acid Synthase, Type II / Q000378:metabolism*; D007538:Isoniazid / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism*; D009171:Mycolic Acids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D009171:Mycolic Acids; D051080:Acyl-Carrier Protein S-Malonyltransferase; C494968:fabD protein, E coli; C554363:Pknk protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases; D054889:Fatty Acid Synthase, Type II; D007538:Isoniazid