Ann Clin Microbiol 2025;28(4):26. Drug susceptibility testing for Mycobacterium tuberculosis: a narrative review
| WHO category | Drug or drug class | Resistance gene | Gene function | Mechanism of drug resistance |
|---|---|---|---|---|
| First-line agents | Rifampicin | rpoB | RNA polymerase | Target modification |
| Isoniazid | katG | Catalase-peroxidase enzyme | Decreased drug activation | |
| inhA | NADH-dependent enoyl-acyl carrier protein | Target amplification or modification | ||
| Pyrazinamide | pncA | Pyrazinamidase | Decreased drug activation | |
| panD | Aspartate decarboxylase | Unknown | ||
| rpsA | Ribosomal protein S1 | Target modification | ||
| Ethambutol | embCAB operon | Arabinosyl transferase | Target modification | |
| ubiA | Arabinogalactan synthesis | Gain-of-function | ||
| Group A | Levofloxacin | gyrA | DNA gyrase A | Target modification |
| Moxifloxacin | gyrB | DNA gyrase B | Target modification | |
| Bedaquiline | atpE | ATP synthase | Target modification | |
| pepQ | Putative Xaa-Pro aminopeptidase | Unknown | ||
| Rv0678 | Transcriptional regulator of mmpL5 | Drug efflux | ||
| Linezolid | rrl | 23S rRNA | Target modification | |
| rplC | 50S ribosomal protein L3 | Target modification | ||
| Group B | Clofazimine | pepQ | Putative Xaa-Pro aminopeptidase | Drug efflux |
| Rv0678 | Transcriptional regulator of mmpL5 | Drug efflux | ||
| Cycloserine/Terizidone | ald | L-alanine dehydrogenase | Substrate shunting | |
| alr | Alanine racemase | Target modification | ||
| ddl | D-alanine-D-alanine ligase | Target modification | ||
| cycA | D-serine/L- & D-alanine/glycine/D-cycloserine proton symporter | Mechanism not confirmed | ||
| Group C | Delamanid/Pretomanid | ddn | Oxidative stress | Decreased drug activation |
| fgd1 | Glucose-6-phosphate oxidation | Decreased drug activation | ||
| Imipenem/cilastatin | crfA | Unknown | Drug inactivation | |
| Injectables | rrs | 16S rRNA | Target modification | |
| Streptomycin | rpsL | 12S ribosomal protein | Target modification | |
| rrs | 16S rRNA | Target modification | ||
| gidB | 7-Methylguanosine methyltransferase | Target modification | ||
| Ethionamide (Prothionamide) | ethA | Mono-oxygenase | Decreased drug activation | |
| ethR | Transcriptional regulatory repressor protein | Decreased drug activation | ||
| inhA | NADH-dependent enoyl-acyl carrier protein | Target amplification or modification | ||
| Other medicines | Kanamycin | eis | Aminoglycoside acetyltransferase | Inactivating mutation |
| Capreomycin | tlyA | rRNA methyltransferase | Target modification |
Abbreviations: WHO, World Health Organization; NADH, nicotinamide adenine dinucleotide (reduced form); ATP, adenosine triphosphate.