KatG

KatG is the catalase-peroxidase enzyme commonly studied in bacteria, most notably in Mycobacterium tuberculosis. It is a heme-containing protein encoded by the katG gene and functions as part of the organism’s defense against oxidative stress. KatG exhibits both catalase activity, breaking down hydrogen peroxide into water and oxygen, and peroxidase activity, driving the oxidation of a range of substrates in the presence of peroxides. This dual functionality helps bacteria withstand reactive oxygen species produced by host immune defenses.

In Mycobacterium tuberculosis, KatG also plays a central role in the activation of the antitubercular prodrug isoniazid (INH). Isoniazid is converted by KatG into active species that inhibit mycolic acid synthesis, a critical component of the mycobacterial cell wall. This activation step makes KatG a key determinant of isoniazid efficacy. Mutations in katG can disrupt prodrug activation while preserving catalase activity, enabling the bacterium to survive INH treatment.

The most common clinically relevant mutations occur at residues such as Ser315, leading to isoniazid resistance. Because of its involvement in drug activation, katG status is frequently assessed in molecular diagnostics to help determine INH resistance patterns in TB isolates, alongside other resistance markers.

KatG homologs are present in a variety of bacteria, where the enzyme generally contributes to oxidative stress defense. In MTB, however, its unique role in activating isoniazid makes it a focal point of TB biology, treatment, and drug-resistance research.