title: Coresistance to isoniazid and ethionamide maps to mycothiol biosynthetic genes in Mycobacterium bovis.
abstract: A search to identify new mechanisms of isoniazid resistance in Mycobacterium bovis led to the isolation of mutants defective in mycothiol biosynthesis due to mutations in genes coding for the glycosyltransferase (mshA) or the cysteine ligase (mshC). These mutants showed low-level resistance to isoniazid but were highly resistant to ethionamide. This study further illustrates that mutations in mycothiol biosynthesis genes may contribute to isoniazid or ethionamide resistance across mycobacterial species.
authors.affiliation: Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Ave., Bronx, NY 10461, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vilchèze
authors.forename: Yossef
authors.initials: Y
authors.lastname: Av-Gay
authors.forename: S Whitney
authors.initials: SW
authors.lastname: Barnes
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Larsen
authors.forename: John R
authors.initials: JR
authors.lastname: Walker
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Glynne
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000096:biosynthesis / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005000:Ethionamide / Q000494:pharmacology*; D006020:Glycopeptides / Q000096:biosynthesis / Q000235:genetics*; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D007294:Inositol / Q000096:biosynthesis / Q000235:genetics*; D007538:Isoniazid / Q000494:pharmacology*; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D006020:Glycopeptides; C089265:mycothiol; D007294:Inositol; D016695:Glycosyltransferases; D013437:Carbon-Sulfur Lyases; C019971:cysteine lyase; D003545:Cysteine; D005000:Ethionamide; D007538:Isoniazid