inhA , a Gene Encoding a Target for Isoniazid and Ethionamide in Mycobacterium tuberculosis

American Association for the Advancement of Science (AAAS) - Tập 263 Số 5144 - Trang 227-230 - 1994
Asesh Banerjee1, Eugenie Dubnau1, Annaı̈k Quémard1, V. Balasubramanian1, Kyung Sun Um1, Theresa Wilson2, Desmond M. Collins2, Geoffrey de Lisle2, William R. Jacobs1
1Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
2AgResearch, Wallaceville Animal Research Center, Upper Hutt, New Zealand.

Tóm tắt

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.

Từ khóa


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