Mechanisms of drug resistance in Mycobacterium tuberculosis
| Antimycobacterial agent | Mechanism of action | Genes involved in resistance | Frequency of mutations associated with resistance | Mechanism of resistance | |||
|---|---|---|---|---|---|---|---|
| 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 | |||