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

Asesh Banerjee, Eugenie Dubnau, Annaik Quemard, V. Balasubramanian, Kyung Sun Um, Theresa Wilson, Des Collins, Geoffrey De Lisle, William R. Jacobs

Research output: Contribution to journalArticle

1090 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)227-230
Number of pages4
JournalScience
Volume263
Issue number5144
DOIs
StatePublished - Jan 14 1994

ASJC Scopus subject areas

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    Banerjee, A., Dubnau, E., Quemard, A., Balasubramanian, V., Um, K. S., Wilson, T., Collins, D., De Lisle, G., & Jacobs, W. R. (1994). inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science, 263(5144), 227-230. https://doi.org/10.1126/science.8284673