Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity, oxidizing various electron donors including NADP(H) (PubMed:9006925, PubMed:18178143). Protects M.tuberculosis against toxic reactive oxygen species (ROS) including hydrogen peroxide as well as organic peroxides and thus contributes to its survival within host macrophages by countering the phagocyte oxidative burst (PubMed:8658136, PubMed:15165233). Also displays efficient peroxynitritase activity, which may help the bacterium to persist in macrophages (PubMed:10080924). Might be involved in DNA repair. Partly complements recA-deficient E.coli cells exposed to UV radiation, mitomycin C or hydrogen peroxide. Increases resistance to mitomycin C in E.coli cells deficient for either uvrA, uvrB or uvrC. Catalyzes the oxidative activation of the antitubercular pro-drug isoniazid (INH) to generate an isonicotinoyl radical that then reacts nonenzymatically with NAD to form an isonicotinoyl-NAD adduct which inhibits InhA. AH2 + H2O2 = A + 2 H2O 2 H2O2 = 2 H2O + O2 Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit. kcat is 10100 sec(-1) for the catalase reaction (at pH 7.0 and 25 degrees Celsius). Optimum pH is 7.0 for the catalase activity and 4.5-5.5 for the peroxidase activity (PubMed:9006925). Optimum pH is 4.75 for the peroxidase activity (PubMed:18178143). Homodimer. By treatment with H(2)O(2) (PubMed:8658136). Repressed by FurA (PubMed:11401695). Consists of two related domains. The catalase-peroxidase activity is associated with the N-terminal domain but no definite function has been assigned to the C-terminal domain, although it may play a role in substrate binding. Formation of the three residue Trp-Tyr-Met cross-link is important for the catalase, but not the peroxidase activity of the enzyme (By similarity). The formation of the Trp-Tyr-Met cross-link is autocatalytic (PubMed:15840564). Cells lacking this gene are devoid of catalase activity, supersensitive to H(2)O(2) exposure and highly resistant to the antitubercular drug isoniazid (INH) in vitro. This mutant strain is markedly attenuated for virulence in mice and displays impaired growth in infected macrophages, but its growth and survival is indistinguishable from wild-type in macrophages lacking the ROS-generating NADPH oxidase (Phox). In contrast to the Synechocystis sp. enzyme, no Trp radical is formed on the distal Trp residue (Trp-91). Was identified as a high-confidence drug target. Many isoniazid-resistant clinical isolates contain mutations in katG, leading to abolition or reduction of catalase/peroxidase activity which results in lack of INH activation, or to a reduced affinity for INH. Other mechanisms of INH resistance include deletion of the katG gene, and down-regulation of katG expression due to mutations in the furA-katG intergenic region. Belongs to the peroxidase family. Peroxidase/catalase subfamily.