[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.
Genes asociados con resistencia a medicamentos anti-tuberculosos Antibiotico Gen Mecanismo de accion Codifica para la enzima katG
catalasa-peroxidasa: transforma la INH en el principio activo, inhibiendo la sintesis del acido micolico isoniazida inhA Codifica la sintesis de la proteina enoil ACP reductasa, implicada en la produccion de acidos grasos de la micobacteria Codifica para la subunidad p de rifampicina rpoB la RNA polimerasa, a la cual se une la rifampicina, interfiriendo en la sintesis del acido nucleico en el proceso de replicacion bacteriana Fluoroquinolonas gyrA/gyrB Inhiben la actividad de la ADN girasa.
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%  Isoniazid katG
, inhA, 84%  ahpC-oxyR Ethambutol embB 70%  Streptomycin rrs, rpsL 60%-70%  Pyrazinamide pncA 72%-99%  Fluoroquinolones gyrA  87% (Moxifloxacin) 83% (Ofloxacin) Aminoglycosides rrs  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] 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] 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.
Isoniazid is a prodrug that is converted to an active intermediates (Isonicotinoyl acyl radical) by the catalase-peroxidase enzyme encoded by the katG
gene of M.
Patterns of Amino Acid Changes and Mutations in katG
Ki, "Characterization of a novel catalaseperoxidase (KATG
) gene from the dinoflagellate Prorocentrum minimum," Journal of Phycology, vol.
The two mutation probes for the katG
gene detected mutations at the codons S315T1 (katG
MUT1) and S315T2 (katG
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.