Microbial peroxidase and related bacterial redox enzymes (KatG/AhpC)

Microbial peroxidases and related redox enzymes, most notably the catalase-peroxidase KatG, are critical components of the bacterial defense system against oxidative stress. These enzymes catalyze the decomposition of hydrogen peroxide and other reactive oxygen species, protecting the pathogen from host-mediated immune attacks. In the context of pharmacology, KatG is uniquely significant as the primary activator of the frontline anti-tuberculosis drug Isoniazid. Mutations in the genes encoding these enzymes, particularly katG, are the most common mechanism of high-level resistance in Mycobacterium tuberculosis. Beyond KatG, related enzymes like alkyl hydroperoxide reductase (AhpC) often compensate for the loss of peroxidase activity in resistant strains, maintaining bacterial viability under stress.

Other names

Catalase-peroxidaseKatGAlkyl hydroperoxide reductaseAhpCBacterial peroxidaseHeme-dependent peroxidaseNADH-dependent peroxidase

Isoniazid is a prodrug that must be activated by the bacterial catalase-peroxidase enzyme (KatG) to form an isonicotinyl-NAD adduct, which then inhibits InhA (enoyl-ACP reductase), blocking mycolic acid synthesis.