Table 2.
Mutations in bedaquiline candidate genes occurring in at least 5 samples and more than one independent clade.
| Mutation | Gene | Freq | Sub-lineage (# isolates) | # sub-lineages | Max SNP dist.* | # Independent Occurrences | Susc. % | MDR or XDR % | Pre-2014%** | Functional support*** |
|---|---|---|---|---|---|---|---|---|---|---|
| -11C > A | mmpR5 | 124 | 2.2.1(122); 4.3.2.1(1); 1.1.1(1) | 3 | 207 | 3 | 12.1 | 76.6 | 93.1 | - |
| 192_193insG (I67fs) | mmpR5 | 44 | 4(34); 2.2.1(4); 3(2); 4.9(1); 4.8(1); 4.5(1); 1.1.1(1) | 7 | 60 | 10 | 0 | 86.4 | 100 | - |
| G197R | pepQ | 38 | 4.3.4.1(37); 2.2.1(1) | 2 | 168 | 2 | 52.6 | 47.4 | 72.2 | S,P |
| K94N | pepQ | 23 | 3.1.1(22); 4.1.2(1) | 2 | 24 | 2 | 95.7 | 0 | 100 | - |
| M146T | mmpR5 | 21 | 4.4.1.1(20); 2.2.2(1) | 2 | 11 | 2 | 0 | 100 | - | S,M |
| D5G | mmpR5 | 18 | 2.2.1(17); 4.1.2.1(1) | 2 | 33 | 2 | 94.4 | 0 | 75.0 | - |
| 193_193del (I67fs) | mmpR5 | 16 | 4.3.4.2(10); 2.2.1(3); 4.7(2); 4.3.3.1(1) | 4 | 17 | 5 | 0 | 100 | 83.3 | - |
| 141_142insC | mmpR5 | 15 | 2.2+(8); 4.1.2+(2); 4.3+(2); 4.4.1.1(1); 3(2) | 8 | - | 11 | 6.7 | 86.7 | 85.7 | - |
| V20A | mmpR5 | 10 | 4.1.2.1(8); 4.3.2.1(1); 2.2.1(1) | 3 | 23 | 3 | 90 | 10 | 83.3 | M |
| L117R | mmpR5 | 9 | 3(5); 4.3.4.2(2); 4.2.2(1); 4.1(1) | 4 | 98 | 5 | 44.4 | 44.4 | 100 | S |
| L32S | mmpR5 | 8 | 2.2.1(8) | 1 | 21 | 3 | 0 | 87.5 | 50 | S,M |
| G121R | mmpR5 | 7 | 2.2.2(5); 3(1); 4.4.1.1(1) | 3 | 4 | 3 | 0 | 100 | 100 | S,P |
| D141H | mmpR5 | 7 | 2.2.1(6); 1.1.3(1) | 2 | 130 | 2 | 14.3 | 57.1 | 100 | S,P |
| R90C | mmpR5 | 7 | 2.2.1(6); 4.1.1.3(1) | 2 | 24 | 4 | 85.7 | 0 | 50 | - |
| N98D | mmpR5 | 5 | 4.1.2.1(2); 4.4.1.1(2); 2.2.1(1) | 3 | 5 | 3 | 0 | 80 | 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 BDQ in previous studies in bold; mutations associated with susceptibility to BDQ underlined (see S3 Table).