Table 4.
Mutations associated with bedaquiline resistance in NTM species
| Gene | Mutation in amino acid | Mutation in DNA | MIC (mg/L) | No. of isolates | Mycobacterium species | Type of isolate | Study (year) |
|---|---|---|---|---|---|---|---|
| atpE | Ala35Ala | T105C | 0.031 | 3 | M. abscessus | Clinical | Pang et al. (2017)40 |
| 0.62 | 5 | ||||||
| 0.125 | 5 | ||||||
| 0.25 | 2 | ||||||
| 2 | 1 | ||||||
| 4 | 1 | ||||||
| Ala63Met | >2 | 2 | M. flavescens | Clinical | Aguilar-Ayala et al. (2017)6 | ||
| 8 | 1 | M. novocastrense | Clinical | ||||
| 8 | 1 | M. shimoidei | Clinical | Huitric et al. (2007)32 | |||
| 4 | 1 | M. xenopi | Clinical | ||||
| 8 | 1 | ||||||
| 0.5 | 1 | M. smegmatis | Non-clinical | Segala et al. (2012)47 | |||
| Ala63Pro | 0.5 | 1 | M. smegmatis | Non-clinical | Segala et al. (2012)47 | ||
| 16 | 1 | M. abscessus | Non-clinical | ||||
| Ala64Pro | 16 | 1 | M. abscessus | Non-clinical | Dupont et al. (2017)29 | ||
| 0.125 | 1 | ||||||
| Ala65Pro | 0.004 | 1 | M. intracellulare | Clinical on treatment | Alexander et al. (2017)62 | ||
| 2 | 1 | M. intracellulare | Clinical post treatment | ||||
| 2 | 1 | M. intracellulare | Clinical on treatment | ||||
| Aps32Gly | T32C | >0.5 | 1 | M. smegmatis | Non-clinical | Maeda et al. (2021)38 | |
| Asp28Ala | 8 | 7 | M. abscessus | Non-clinical | Segala et al. (2012)47 | ||
| 4 | 9 | M. fortuitum | Non-clinical | ||||
| 16 | 1 | M. smegmatis | Non-clinical | ||||
| Asp28Gly | >16 | 1 | M. smegmatis | Non-clinical | Segala et al. (2012)47 | ||
| Asp28Val | 16 | 1 | M. smegmatis | Non-clinical | Segala et al. (2012)47 | ||
| Asp776Asn & Asp32Ala & Gly31Gly | G776A & T32G & G31A | 0.19 | 1 | M. smegmatis | Non-clinical | Maeda et al. (2021)38 | |
| Asp32Ala & Gly31Gly & Ser465Pro | T32G & G31A & T465C | 0.25 | 1 | M. smegmatis | Non-clinical | ||
| Asp29Val | 16 | 1 | M. abscessus | Non-clinical | Dupont et al. (2017)29 | ||
| 0.125 | 1 | ||||||
| Asp32Val | MIC90 = 3 | 1 | M. smegmatis | Non-clinical | Andries et al. (2014)24 | ||
| MIC90 = 3 | 1 | ||||||
| Glu61Asp | 4 | 1 | M. smegmatis | Non-clinical | Segala et al. (2012)47 | ||
| Glu65Glu | A195G | 0.062 | 2 | M. fortuitum | Clinical | Pang et al. (2017)40 | |
| 0.25 | 1 | ||||||
| 1 | 1 | ||||||
| 16 | 1 | ||||||
| Glu65Asp | T65A | 0.5 | 1 | M. smegmatis | Non-clinical | Maeda et al. (2021)38 | |
| Gly24Gly | T72C | 0.062 | 6 | M. abscessus | Clinical | Pang et al. (2017)40 | |
| 0.12 | 8 | ||||||
| 0.25 | 4 | ||||||
| 0.5 | 6 | ||||||
| >16 | 1 | ||||||
| Gly49Gly | C147T | 0.0156 | 6 | M. intracellulare | Clinical | Pang et al. (2017)40 | |
| 0.031 | 2 | ||||||
| 0.062 | 3 | ||||||
| 0.12 | 2 | ||||||
| 1 | 1 | ||||||
| 4 | 1 | ||||||
| >16 | 1 | ||||||
| Gly62Gly | T186C | 0.031 | 2 | M. kansasii | Clinical | Pang et al. (2017)40 | |
| 0.063 | 3 | ||||||
| 1 | 1 | ||||||
| Ile66Met | 8 | 1 | M. smegmatis | Non-clinical | Segala et al. (2012)47 | ||
| 16 | 8 | ||||||
| Leu59Val | 0.5 | 1 | M. smegmatis | Non-clinical | Segala et al. (2012)47 | ||
| Val62Val | C186A | 0.031 | 1 | M. avium | Clinical | Pang et al. (2017)40 | |
| C186T | 0.062 | 1 | |||||
| C186A | 0.12 | 1 | |||||
| C186A | >16 | 1 | |||||
| Wild type | 0.004–0.03 (0.025) | 22 | M. intracellulare | Clinical | Alexander et al. (2017)62 | ||
| <0.003 | 1 | M. avium | Clinical | Zweijpfenning et al. (2019)68 | |||
| No non-synonymous mutation was found | 0.0078–1 | 197 | M. abscessus | Clinical | Li et al. (2018)34 | ||
| mmpT5 | WT | 0.004 | 5 | M. intracellulare | Clinical | Alexander et al. (2017)62 | |
| Gly66FS | C196_197insC | 0.008 | 1 | M. intracellulare | Clinical | ||
| Val46Gly | T137G | 0.025 | 2 | M. intracellulare | Clinical | ||
| Glu177Lys | G529A | 0.004 | 1 | M. intracellulare | Clinical | ||
| 0.008 | 2 | ||||||
| 0.025 | 1 | ||||||
| Ala23Pro &Glu177Lys | G67C & G529A | 0.008 | 2 | M. intracellulare | Clinical | ||
| Pro104FS | C311_312insC | 0.015 | 2 | M. intracellulare | Clinical | ||
| 0.025 | 2 | ||||||
| Ala162Pro | G484C | 0.004 | 1 | M. intracellulare | Clinical | ||
| 0.008 | 1 | ||||||
| Ilu19Ser & Glu177Lys | T56G & G529A | 0.008 | 1 | M. intracellulare | Clinical | ||
| Val35Gly & Glu177Lys | T104G & G529A | 0.008 | 1 | M. intracellulare | Clinical | ||
| Arg25Pro | G74C | 0.004 | 1 | M. intracellulare | Clinical | ||
| MAB_4384 | Ala152 Glu | 0.062 | 2 | M. abscessus | Clinical | Li et al. (2018)34 | |
| Ala169 Ser | 0.5 | 1 | M. abscessus | Clinical | |||
| Del (MAB_4384 gene) | Del | 0.0078 | 2 | M. abscessus | Clinical | ||
| 0.0156 | 3 | ||||||
| 0.031 | 18 | ||||||
| 0.062 | 39 | ||||||
| 0.125 | 36 | ||||||
| 0.25 | 11 | ||||||
| Gln215 Arg | 0.0078 | 1 | M. abscessus | Clinical | |||
| 0.031 | 1 | ||||||
| 0.062 | 1 | ||||||
| 0.125 | 4 | ||||||
| 0.5 | 1 | ||||||
| Gly125 Asp & Gln215 Arg | 0.062 | 1 | M. abscessus | Clinical | |||
| 0.125 | 2 | ||||||
| His7 Arg &Glu142 Lys | 0.125 | 1 | M. abscessus | Clinical | |||
| 0.25 | 4 | ||||||
| 0.5 | 1 | ||||||
| N1T | 0.062 | 2 | M. abscessus | Clinical | |||
| 0.125 | 1 | ||||||
| WT | 0.007 | 2 | M. abscessus | Clinical | |||
| 0.015 | 1 | ||||||
| 0.031 | 9 | ||||||
| 0.062 | 16 | ||||||
| 0.125 | 19 | ||||||
| 0.25 | 6 | ||||||
| 0.5 | 2 | ||||||
| 1 | 1 | ||||||
| Trp88 Gly | 0.062 | 2 | M. abscessus | Clinical | |||
| 0.125 | 1 | ||||||
| Val31 Ile | 0.031 | 1 | M. abscessus | Clinical | |||
| 0.125 | 2 | ||||||
| 0.25 | 1 | ||||||
| Val31 IleI & Asp120 Asn | 1 | M. abscessus | Clinical | ||||
| Val5 Met & His7 Arg & Glu142 Lys & Ala217 Ser | 1 | M. abscessus | Clinical | ||||
| MAB_2299c | Asp106fs | ins318A | 2 | 1 | M. abscessus | Non-clinical | Richard et al. (2018)43 |
| Glu181stop | C276 | 2 | 1 | ||||
| Gly215Ser | G541T | 2 | 1 | ||||
| Leu151Pro | G643A | 2 | 1 | ||||
| Leu40Trp | T452C | 2 | 1 | ||||
| Pro92fs | T119G | 2 | 1 | ||||
| MAV_2152 | Trp173Arg | A2544950G | 0.06 | 1 | M. avium | Clinical | Zweijpfenning et al. (2019)68 |
| Trp173Arg | A2544950G | 0.125 | 1 | ||||
| rpoB | Asp 776Asn | 0.5 | 1 | M. smegmatis | Non-clinical | Maeda et al. (2021)38 | |
| prpE | Ser465Pro | 0.2 | 1 | M. smegmatis | Non-clinical |