Table 3.
Nucleotide and amino acid changes identified in the specific region of six M. tuberculosis drug-resistant associated loci for the corresponding antibiotic
| Locus (no. of resistant isolates tested) | Drug | Codon(s) | Changea |
No. (%) of isolates | Other mutation | |
|---|---|---|---|---|---|---|
| Nucleotide | Amino acid | |||||
| rpoBb (77) | RIF | Nonec | None | None | 4 (5.2) | |
| 505 | TTC→TTT | Phe→Phef | 1 (1.3) | |||
| 511 | CTG→CCG | Leu→Pro | 3 (3.9) | |||
| 514 | TTC→Inse | Phe→Ins | 1 (1.3) | |||
| 516 | GAC→TAC | Asp→Tyr | 1 (1.3) | |||
| GAC→GTC | Asp→Val | 4 (5.2) | ||||
| GAC→TTC | Asp→Phe | 1 (1.3) | ||||
| 526 | CAC→AAC | His→Asn | 2 (2.6) | |||
| CAC→TAC | His→Tyr | 3 (3.9) | ||||
| CAC→CTC | His→Leu | 2 (2.6) | ||||
| CAC→GAC | His→Asp | 7 (9.1) | ||||
| CAC→CGC | His→Arg | 2 (2.6) | ||||
| CAC→TGC | His→Cys | 2 (2.6) | ||||
| 529 | CGA→AAA | Arg→Lys | 1 (1.3) | |||
| 531 | TCG→TTG | Ser→Leu | 29 (37.6) | |||
| 511/515d | CTG→CCG | Leu→Pro | 1 (1.3) | |||
| ATG→GTG | Met→Val | |||||
| 511/516 | CTG→CCG | Leu→Pro | 2 (2.6) | |||
| GAC→GGC | Asp→Gly | |||||
| 511/516 | CTG→CCG | Leu→Pro | 1 (1.3) | |||
| GAC→GCC | Asp→Ala | |||||
| 511/516 | CTG→CCG | Leu→Pro | 1 (1.3) | |||
| GAC→AAC | Asp→Asn | |||||
| 513/561 | CAA→GAA | Gln→Glu | 1 (1.3) | |||
| ATC→GTC | Ile→Val | |||||
| 516/572 | GAC→GGC | Asp→Gly | 1 (1.3) | |||
| ATC→CTC | Ile→Leu | |||||
| 516/572 | GAC→TAC | Asp→Tyr | 1 (1.3) | |||
| ATC→ATG | Ile→Met* | |||||
| 531/525 | TCG→TTG | Ser→Leu | 1 (1.3) | |||
| ACC→ACA | Thr→Thrf | |||||
| 531/569 | TCG→TTG | Ser→Leu | 1 (1.3) | |||
| ATC→GTC | Ile→Val* | |||||
| 531/584 | TCG→TTG | Ser→Leu | 2 (2.6) | |||
| TTC→TCC | Phe→Ser* | |||||
| 515/526/535 | ATG→GTG | Met→Val | 1 (1.3) | |||
| CAC→AAC | His→Asn | |||||
| CCC→TCC | Pro→Ser | |||||
| 531/615/626 | TCG→TTG | Ser→Leu | 1 (1.3) | |||
| GTG→ATG | Val→Met* | |||||
| GAC→GAG | Asp→Glu* | |||||
| katG (77) | INH | None | None | None | 16 (20.8) | |
| None | None | None | 5 (6.5) | –15C→T upstream of mabA | ||
| None | None | None | 1 (1.3) | –8T→A upstream of mabA | ||
| 191 | TGG→CGG | Trp→Arg | 1 (1.3) | |||
| TGG→TGA | Trp→Stop* | 1 (1.3) | ||||
| 271 | ACT→CCT | Thr→Pro* | 2 (2.6) | –15C→T upstream of mabA | ||
| 299 | GGC→TGC | Gly→Cys | 1 (1.3) | |||
| GGC→AGC | Gly→Ser | 2 (2.6) | ||||
| 315 | AGC→ACC | Ser→Thr | 36 (46.8) | |||
| AGC→ACC | Ser→Thr | 2 (2.6) | –15C→T upstream of mabA | |||
| AGC→ACC | Ser→Thr | 2 (2.6) | –8T→C upstream of mabA | |||
| AGC→AAC | Ser→Asn | 1 (1.3) | –8T→C upstream of mabA | |||
| AGC→ACA | Ser→Thr | 3 (3.9) | ||||
| AGC→CGC | Ser→Arg | 1 (1.3) | ||||
| AGC→ATC | Ser→Ile | 1 (1.3) | ||||
| 327 | AAA→AAG | Lys→Lysf | 1 (1.3) | |||
| 328 | TGG→TTT | Trp→Phe* | 1 (1.3) | |||
| mabA-inhA (77) | INH | None | None | None | 64 (83.1) | |
| –8T→A | 1 (1.3) | |||||
| –8T→C | 2 (2.6) | AGC315ACC (Ser→Thr) in katG | ||||
| –8T→C | 1 (1.3) | AGC315AAC (Ser→Asn) in katG | ||||
| –15C→T | 5 (6.5) | |||||
| –15C→T | 2 (2.6) | ATC271CCT (Thr→Pro) in katG | ||||
| –15C→T | 2 (2.6) | AGC315ACC (Ser→Thr) in katG | ||||
| gyrA (39) | OFX | None | None | None | 1 (2.6) | |
| 21/95 | GAG→CAG | Glu→Gln | 5 (12.8) | |||
| AGC→ACC | Ser→Thr | |||||
| 21/95 | GAG→CAG | Glu→Gln | 1 (2.6) | GAC500CAC (Asp→His) in gyrB | ||
| AGC→ACC | Ser→Thr | |||||
| 21/95/90 | GAG→CAG | Glu→Gln | 3 (7.7) | |||
| AGC→ACC | Ser→Thr | |||||
| GCG→GTG | Ala→Val | |||||
| 21/95/91 | GAG→CAG | Glu→Gln | 2 (5.1) | |||
| AGC→ACC | Ser→Thr | |||||
| TCG→CCG | Ser→Pro | |||||
| 21/95/94 | GAG→CAG | Glu→Gln | 19 (48.7) | |||
| AGC→ACC | Ser→Thr | |||||
| GAC→GGC | Asp→Gly | |||||
| 21/95/94 | GAG→CAG | Glu→Gln | 5 (12.8) | |||
| AGC→ACC | Ser→Thr | |||||
| GAC→AAC | Asp→Asn | |||||
| 21/95/94 | GAG→CAG | Glu→Gln | 1 (2.6) | |||
| AGC→ACC | Ser→Thr | |||||
| GAC→GCC | Asp→Ala | |||||
| 21/95/94 | GAG→CAG | Glu→Gln | 1 (2.6) | |||
| AGC→ACC | Ser→Thr | |||||
| GAC→TAC | Asp→Tyr | |||||
| 21/95/94 | GAG→CAG | Glu→Gln | 1 (2.6) | GAA540GAC (Glu→Asp) in gyrB | ||
| AGC→ACC | Ser→Thr | |||||
| GAC→GCC | Asp→Ala | |||||
| gyrB (39) | OFX | None | None | None | 37 (94.8) | |
| 500 | GAC→CAC | Asp→His | 1 (2.6) | |||
| 540 | GAA→GAC | Glu→Asp | 1 (2.6) | GAC94GCC (Asp→Ala) in gyrA | ||
| rrs (19) | KAN, CAP | None | None | None | 2 (10.5) | |
| CAP | None | None | None | 1 (5.3) | ||
| KAN, AMK, CAP | None | None | None | 1 (5.3) | ||
| KAN, AMK | 1401A→G | 6 (31.6) | ||||
| KAN, AMK, CAP | 1401A→G | 8 (42.1) | ||||
| KAN, AMK, CAP | 1402C→T | 1 (5.3) | ||||
*, Mutations not previously reported.
The amino acid numbering is based on homologous mutations in E. coli.
None, no mutation.
Multiple mutations in one isolate.
Ins, insertion.
Silent mutation.