The purpose of these studies is ultimately to develop better tuberculosis drugs. Our studies of isoniazid resistance identified two enzymes, Ndh and InhA, that are likely to be essential in M. tuberculosis and are apt to be good drug targets. InhA is a terrific candidate for new drug development since it is a known target for isoniazid. The Ndh enzyme is not essential in the facultative anaerobes such as Escherichia coli because these organisms have multiple pathways for NADH oxidation. In contrast, the thermosensitive lethality of the M. smegmatis ndh mutants indicates that Ndh is required for viability and is the main enzyme responsible for NADH oxidation (Miesel et al 1998).
Financial support was provided by the NIH grant AI36849. We thank L. Basso, J. Musser and J. Blanchard for providing data prior to publication.
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