Interventions for Tuberculosis Control and Elimination 2002

emain elusive, 47 the general mechanism of action is fairly well understood
(figure 6). 46 Several mutations have been identified which confer resistance
in M. tuberculosis. Important mutations are located on the katG
gene, 41 and the inhA gene, 48 of which the latter is responsible for approximately
25% of clinical isolates that demonstrate resistance, generally associated
with low-levels of resistance. Susceptibility to isoniazid is dependent
on the presence of the catalase-peroxidase enzyme encoded by the
katG gene. 44,49 Mutations in catalase-peroxidase lead to high-level isoniazid
resistance. 41,50 The ahpC gene encodes the alkyl hydroperoxide reductase,
and its absence leads to isoniazid resistance. 51 Approximately 60%
to 70% of isoniazid resistant strains carry mutations in one of several genes
involved in its activation from pro-drug (katG and possibly ahpC) or in the
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Figure 6. The proposed action of isoniazid. Reproduced from 46 by the permission
of the publisher ASM Press.