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Updated: Jul 25, 2026

A Microscopic Phenotypic Assay for the Quantification of Intracellular Mycobacteria Adapted for High-throughput/High-content Screening
Published on: January 17, 2014
Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis
D A Rozwarski1, G A Grant, D H Barton
1Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Abstract:
The preferred antitubercular drug isoniazid specifically targets a long-chain enoyl-acyl carrier protein reductase (InhA), an enzyme essential for mycolic acid biosynthesis in Mycobacterium tuberculosis. Despite the widespread use of this drug for more than 40 years, its precise mode of action has remained obscure. Data from x-ray crystallography and mass spectrometry reveal that the mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of nicotinamide adenine dinucleotide bound within the active site of InhA.
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