Isoniazid | Inhibition of mycolic acid biosynthesis | (i) katG(catalase-peroxidase) | (i) 42–58% | (i) Mutations inkatG result in failure to generate an active intermediate of isoniazid |
| | (ii)inhA (enoyl-acyl carrier protein reductase) | (ii) 21–34% | (ii) Over expression ofinhA allows continuation of mycolic acid synthesis |
| | (iii) ahpC (alkyl hydroperoxide reductase) | (iii) 10–15% | (iii)ahpC mutations may just serve as a marker for lesions in katG
|
Rifampicin | Inhibition of transcription |
rpoB (β subunit of RNA polymerase) | 96–98% | Mutations in rpoBprevent interaction with rifampicin |
Streptomycin | Inhibition of protein synthesis | (i)rpsL (ribosomal protein S12) | (i) 52–59% | Mutations prevent interaction with streptomycin. Resistance not associated with mutation inrpsL or rrs is usually low level |
(ii) rrs (16S rRNA) | (ii) 8–21% |
Ethambutol | Inhibition of arabinogalactan and lipoarabinomannan biosynthesis |
embcAB(arabinosyl transferase) | 47–65% | Over expression or mutation of EmbB allow continuation of arabinan biosynthesis. Resistance not associated with EmbB mutation is usually low level |
Pyrazinamide | Unknown |
pncA(pyrazinamidase-nicotinamidase) | 72–97% | Loss of pyrazinamidase activity results in decreased conversion of pyrazinamide to pyrazinoic acid, the putative active moiety |
Fluoroquinolones | Inhibition of the DNA gyrase |
gyrA (DNA gyrase subunit A) | 75–94% | Mutations in gyrA prevent interaction with fluoroquinolones Mutations ingyrB and efflux may contribute to resistance |