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Ethionamide

FIG. 1. Structure of isoniazid (INH) and ethionamide (ETH).

responsible for the isoniazid and ethionamide resistance. Increased expression of wild-type inhA also conferred isoniazid and ethionamide resistance to M. smegmatis. These findings led Banerjee and colleagues to conclude that isoniazid resistance can occur by either increasing the amount of the InhA enzyme or by altering the enzyme target so that it is not inhibited by the active drug form (Banerjee etall994).

Sequence analysis of the inhA locus in clinical isolates of M. tuberculosis identified inhA mutations in about 30% of the isoniazid-resistant strains but not in the isoniazid-sensitive strains (Heym et al 1994, Morris et al 1995, Musser et al 1996, Ristow et al 1995, Telenti et al 1997). Most of these mutations are located in the inhA promoter and several are within the inhA structural gene (L. Basso, personal communication 1998). Many of these inhA mutant strains of M. tuberculosis are also resistant to ethionamide (low level resistance), which is consistent with traits of the M. smegmatis inhA resistance mutants (Banerjee et al 1994, Heym et al 1994).

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