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 Myco bacterium tuberculosis is unknown. A missense mutation within the myco bacterial inhA gene was shown to confer resistance to both INH and eth ionamide (ETH) in M. smegmatis and in M. bovis. The wild-type inhA gen e also conferred INH and ETH resistance when transferred on a multicop y plasmid vector to M. smegmatis and M. bovis BCG. The InhA protein sh ows significant sequence conservation with the Escherichia coli enzyme EnvM, and cell-free assays indicate that it may be involved in mycoli c acid biosynthesis. These results suggest that InhA is likely a prima ry target of action for INH and ETH.