Mechanisms of Isoniazid Resistance inMycobacterium tuberculosis:Enzymatic Characterization of Enoyl Reductase Mutants Identified in Isoniazid‐Resistant Clinical Isolates

Mutants in the structural gene of the inhA-encoded NADH-dependent 2-trans enoyl-acyl carrier protein reductase were identified from isoniazid-resistant clinical isolates of Mycobacterium tuberculosis. Recombinant InhA proteins with defined single amino acid replacements were expressed in Escherichia coli and purified to homogeneity. Steady-state kinetic parameters for wild type (WT) and I16T, I21V, I47T, and I95P mutants of the enoyl reductase...