title: inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis.
abstract: Isoniazid (isonicotinic acid hydrazide, INH) is one of the most widely used antituberculosis drugs, yet its precise target of action on Mycobacterium tuberculosis is unknown. A missense mutation within the mycobacterial inhA gene was shown to confer resistance to both INH and ethionamide (ETH) in M. smegmatis and in M. bovis. The wild-type inhA gene also conferred INH and ETH resistance when transferred on a multicopy plasmid vector to M. smegmatis and M. bovis BCG. The InhA protein shows significant sequence conservation with the Escherichia coli enzyme EnvM, and cell-free assays indicate that it may be involved in mycolic acid biosynthesis. These results suggest that InhA is likely a primary target of action for INH and ETH.
authors.affiliation: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: E
authors.initials: E
authors.lastname: Dubnau
authors.forename: A
authors.initials: A
authors.lastname: Quemard
authors.forename: V
authors.initials: V
authors.lastname: Balasubramanian
authors.forename: K S
authors.initials: KS
authors.lastname: Um
authors.forename: T
authors.initials: T
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Collins
authors.forename: G
authors.initials: G
authors.lastname: de Lisle
authors.forename: W R
authors.initials: WR
authors.lastname: Jacobs
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005000:Ethionamide / Q000378:metabolism / Q000494:pharmacology*; D005798:Genes, Bacterial; D007538:Isoniazid / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009161:Mycobacterium / Q000187:drug effects / Q000235:genetics; D009163:Mycobacterium bovis / Q000187:drug effects / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009171:Mycolic Acids / Q000378:metabolism; D016366:Open Reading Frames; D010088:Oxidoreductases; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D009171:Mycolic Acids; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium; D005000:Ethionamide; D007538:Isoniazid