KATG

[2,9] Although INH resistance is associated with resistance-conferring mutations in multiple genes, katG and inhA account for ~90% of resistance detected by phenotypic DST.

In 106 INH resistant strains, 97(91%) were associated with mutation in katG gene while resistance in 9 (8.4%) strain was due to mutation in the inhA promoter region.

INH, a known anti-TB drug, targets several genes, namely, KATG, NDH, MSH, and NAT, but the primary target with dominant phenotype remains INHA, which encodes enoyl-Acyl-Carrier-Protein (ACP) termed as inhA reductase.

Drug Locus Percentage resistance References accounted for by mutations Rifampicin rpoB 96% [28] Isoniazid katG, inhA, 84% [29] ahpC-oxyR Ethambutol embB 70% [30] Streptomycin rrs, rpsL 60%-70% [28] Pyrazinamide pncA 72%-99% [31] Fluoroquinolones gyrA [32] 87% (Moxifloxacin) 83% (Ofloxacin) Aminoglycosides rrs [33] 70%-80% (Capreomycin and Amikacin) 60% (Kanamycin)

To enlarge the capacity for the detection of drug resistance, the WHO recommends the use of a line-probe assay, the GenoType MTBDR plus assay (Hain Lifescience GmbH, Nehren, Germany), which can identify the Mycobacterium tuberculosis (MTB) complex as well as resistance to rifampicin (RFP) and isoniazid (INH) drugs.[sup][7] The assay detects mutations in the rpoB gene for RFP resistance, katG gene for INH resistance, and inhA regulatory region gene for low-level INH resistance.[sup][8] Subsequently, a new DNA strip assay, GenoType MTBDR sl version 1.0 (Hain Lifescience GmbH, Nehren, Germany), was developed to detect resistance to ethambutol (EMB), fluoroquinolones, and injectable aminoglycosides/cyclic peptides allowing diagnosis of XDR-TB among MDR-TB patients.

Patterns of Amino Acid Changes and Mutations in katG Gene.

The two mutation probes for the katG gene detected mutations at the codons S315T1 (katG MUT1) and S315T2 (katG MUT2).

MAP needs to convert SodA super oxide radicals to hydrogen peroxide to struggle with this local stress and KatG needs MAP proteins to convert this to water and oxygen (Granger et al., 2004; Voskuil et al., 2011).

Deretic, Nitric Oxide Generated from Isoniazid Activation by KatG: Source of Nitric Oxide and Activity Against Mycobacterium tuberculosis, Antimicrob.