inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis.

Article Details

Citation

Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, Collins D, de Lisle G, Jacobs WR Jr

inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis.

Science. 1994 Jan 14;263(5144):227-30.

PubMed ID
8284673 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
EthionamideEnoyl-[acyl-carrier-protein] reductase [NADH]ProteinMycobacterium tuberculosis
Yes
Inhibitor
Details
Polypeptides
NameUniProt ID
Enoyl-[acyl-carrier-protein] reductase [NADH]P9WGR1Details