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.

Keywords

INHAEthionamideMycobacterium smegmatisMycobacterium bovisIsoniazidMycobacterium tuberculosisBiologyMicrobiologyGeneVirologyTuberculosisGeneticsAntibioticsMedicineStreptomycinEthambutol

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Publication Info

Year
1994
Type
article
Volume
263
Issue
5144
Pages
227-230
Citations
1365
Access
Closed

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Asesh Banerjee, Eugenie Dubnau, Annaı̈k Quémard et al. (1994). <i>inhA</i> , a Gene Encoding a Target for Isoniazid and Ethionamide in <i>Mycobacterium tuberculosis</i>. Science , 263 (5144) , 227-230. https://doi.org/10.1126/science.8284673

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DOI
10.1126/science.8284673