title: Point mutations within the fatty acid synthase type II dehydratase components HadA or HadC contribute to isoxyl resistance in Mycobacterium tuberculosis.
abstract: The mechanism by which the antitubercular drug isoxyl (ISO) inhibits mycolic acid biosynthesis has not yet been reported. We found that point mutations in either the HadA or HadC component of the type II fatty acid synthase (FAS-II) are associated with increased levels of resistance to ISO in Mycobacterium tuberculosis. Overexpression of the HadAB, HadBC, or HadABC heterocomplex also produced high-level resistance. These results show that the FAS-II dehydratases are involved in ISO resistance.
authors.affiliation: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier 2 et 1, CNRS UMR 5235, Montpellier, France.
authors.forename: Laila
authors.initials: L
authors.lastname: Gannoun-Zaki
authors.forename: Laeticia
authors.initials: L
authors.lastname: Alibaud
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D054889:Fatty Acid Synthase, Type II / Q000235:genetics*; D015870:Gene Expression; D006836:Hydro-Lyases; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D009171:Mycolic Acids / Q000037:antagonists & inhibitors; D010670:Phenylthiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D017354:Point Mutation; D021122:Protein Subunits / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D009171:Mycolic Acids; D021122:Protein Subunits; C100189:thiocarlide; D010670:Phenylthiourea; D006836:Hydro-Lyases; D054889:Fatty Acid Synthase, Type II