inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis.
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.
Banerjee
A
A
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
Dubnau
E
E
Quemard
A
A
Balasubramanian
V
V
Um
K S
KS
Wilson
T
T
Collins
D
D
de Lisle
G
G
Jacobs
W R
WR
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
D001426:Bacterial Proteins; D009171:Mycolic Acids; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium; D005000:Ethionamide; D007538:Isoniazid