Mechanisms of action of isoniazid

Mol Microbiol. 2006 Dec;62(5):1220-7. doi: 10.1111/j.1365-2958.2006.05467.x. Epub 2006 Oct 27.


For decades after its introduction, the mechanisms of action of the front-line antituberculosis therapeutic agent isoniazid (INH) remained unclear. Recent developments have shown that peroxidative activation of isoniazid by the mycobacterial enzyme KatG generates reactive species that form adducts with NAD(+) and NADP(+) that are potent inhibitors of lipid and nucleic acid biosynthetic enzymes. A direct role for some isoniazid-derived reactive species, such as nitric oxide, in inhibiting mycobacterial metabolic enzymes has also been shown. The concerted effects of these activities - inhibition of cell wall lipid synthesis, depletion of nucleic acid pools and metabolic depression - drive the exquisite potency and selectivity of this agent. To understand INH action and resistance fully, a synthesis of knowledge is required from multiple separate lines of research - including molecular genetic approaches, in vitro biochemical studies and free radical chemistry - which is the intent of this review.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antitubercular Agents / metabolism
  • Antitubercular Agents / pharmacology*
  • Isoniazid / pharmacology*
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / metabolism
  • NAD / metabolism


  • Antitubercular Agents
  • NAD
  • Isoniazid