Table 3.
Mutations in delamanid candidate genes occurring in at least 5 samples and more than one independent clade.
| Mutation | Gene | Freq | Sub-lineage (# isolates) | # sub-lineages | Max SNP distance* | # Independent Occurrences | Susc. % | MDR or XDR % | Pre-2014%** | Functional Support*** |
|---|---|---|---|---|---|---|---|---|---|---|
| K270M | fgd1 | 3136 | 4.1.2 + (3135); 2.2.1(1) | 3 | 1329 | 2 | 70.1 | 18.1 | 84.2 | - |
| -32A > G | fbiC | 639 | 5, 6, Bov(634); 2.2.1(2); 4.3.3(1); 4.2(1); 4.9(1) | 7 | 3264 | 5 | 60.1 | 8.3 | 63.1 | - |
| T273A | fbiC | 626 | 4.8(625); 1.1.1(1) | 2 | 330 | 2 | 97.9 | 0.3 | 93.6 | - |
| K448R | fbiB | 293 | 3(293) | 1 | 496 | 3 | 57.7 | 30.0 | 51.1 | - |
| D113N | ddn | 267 | 5(264); 2.2.1(3) | 2 | 1402 | 2 | 70.7 | 15.4 | 91.7 | - |
| K296E | fgd1 | 162 | 6(161); 4.1.2.1(1) | 2 | 933 | 2 | 87.0 | 3.7 | 85.7 | - |
| I208V | fbiA | 122 | 4.1.2(121); 4.1.2.1(1) | 2 | 524 | 2 | 70.5 | 11.5 | 96.9 | - |
| W678G | fbiC | 96 | 4.3.3(88); 1.1.1(8) | 2 | 87 | 2 | 8.3 | 81.3 | 90.9 | P |
| I128V | fbiC | 79 | 2.2.1(79) | 0 | 91 | 2 | 0 | 81.0 | 100 | - |
| R72W | ddn | 75 | 1.1.2(75) | 1 | 345 | 2 | 76.0 | 10.7 | 70.2 | S,P |
| A31T | fbiB | 71 | 2.2.1(70); 2.2.2(1) | 1 | 238 | 3 | 54.9 | 9.9 | 100 | - |
| G34R | ddn | 47 | 4.3.2(44); 4.3.4.2(3) | 2 | 147 | 2 | 89.3 | 8.5 | 0.0 | S,P |
| -11G > A | fbiC | 37 | 4.1.2.1(31); 4.1.1.3(3); 6(2); 4.4.2(1) | 4 | 244 | 4 | 56.8 | 16.2 | 100 | - |
| -14G > GA | fbiC | 34 | 2.2.1(25); 4.3.4.2.1(9) | 2 | 30 | 2 | 26.5 | 73.5 | 94.7 | - |
| G81S | ddn | 21 | 2.2.2(12); 2.1(9) | 2 | 277 | 2 | 33.3 | 52.4 | 100 | S,P |
| L49P | ddn | 21 | 2.2.1.1(21) | 1 | 226 | 3 | 57.1 | 9.5 | 94.4 | S,P |
| G139R | fbiA | 18 | 2.2.1(17); 1.1.2(1) | 2 | 30 | 2 | 94.4 | 0 | 75.0 | P |
| W20* | ddn | 17 | 4.5(11); 5(6) | 2 | 241 | 2 | 100 | 0 | 75.0 | - |
| K296R | fgd1 | 16 | 4.1.2.1(12); 4.8(3); 4.4.1.1(1) | 3 | 75 | 3 | 18.8 | 31.3 | 37.5 | - |
| D90N | fbiB | 14 | 3(14) | 1 | 419 | 2 | 50.0 | 14.3 | 14.3 | - |
| R265Q | fbiB | 13 | 2.2.1(12); 1.1.2(1) | 2 | 77 | 3 | 30.8 | 0 | 100 | - |
| A178T | fbiA | 10 | 1.2.1(8); 4.5(1); 3(1) | 3 | 141 | 4 | 70 | 0 | 66.7 | - |
| -43G > A | ddn | 9 | 5(4); 4.2.1(3); 2.2.1(2) | 3 | 244 | 3 | 77.8 | 22.2 | 100 | - |
| P131L | ddn | 9 | 4.8(8); 4.3.4.2.1(1) | 2 | 50 | 2 | 88.9 | 0 | 100 | S,P |
| G655S | fbiC | 9 | 2.2.1(8); 4.1.2(1) | 2 | 24 | 2 | 33.3 | 0 | 100 | - |
| R247W | fgd1 | 8 | 3(7); 4.5(1) | 2 | 62 | 2 | 100 | 0 | 50 | P |
| V348I | fbiB | 8 | 2.2.2(7); 4.1(1) | 2 | 17 | 2 | 100 | 0 | 100 | - |
| R304Q | fbiA | 8 | 3(8) | 2 | 203 | 2 | 87.5 | 0 | 50 | - |
| G325S | fbiB | 7 | 2.2.1(5); 4.9(1); 4.1.2.1(1) | 3 | 63 | 3 | 100 | 0 | 83.3 | - |
| P182L | fbiB | 6 | 4.3.4.2.1(3); 6(3) | 2 | 320 | 2 | 66.7 | 16.7 | 100 | - |
| M93I | fgd1 | 6 | 4.9(3); 4.1.2.1(2); 2.2.1(1) | 3 | 3 | 3 | 83.3 | 0 | - | - |
| P45L | ddn | 5 | 4.4.1.1(3); 3(1);1.1.1(1) | 3 | 63 | 3 | 80 | 0 | 100 | S,P |
| L326F | fbiB | 5 | 4.6.1.1(2); 4.1.2+(2); 4.8(1) | 4 | - | 4 | 100 | 0 | - | - |
| T455A | fbiC | 5 | 3(4); 1.1.1(1) | 2 | 236 | 2 | 80 | 0 | 100 | - |
Sub-lineages: + = more than 1 sub-lineage; # = number; * Maximum SNP distance calculated in clades of ≥ 5 isolates; Drug resistance (%): Susc. = Susceptible; ** % of number of samples pre-2014/total number of samples with available collection date; *** Functional support: S = snap2 score ≥ 50; P = Provean Score ≤ −4; M = mCSM predicted stability change (ΔΔG) below − 2; Mutations associated with increased MIC for DLM/PTM in previous studies in bold; mutations associated with susceptibility to DLM/PTM underlined (see S3 Table).