TABLE 3.
EMB resistance-associated mutations in M. tuberculosis
| Gene or gene region | No. of isolates with mutations
|
% of isolates with single-locus mutation | MIC rangea (μg/ml) | |
|---|---|---|---|---|
| Single locusb | Multiple loci | |||
| embC | 0 | 2 | 0 | |
| embC-embA intergenic region | 0 | 8 | 0 | |
| embA | 4 | 5 | 5.3 | 10–30 |
| embB | 26 | 15 | 34.7 | 10–50 |
| embR | 2 | 0 | 2.7 | 20–40 |
| Rv3124 | 0 | 3 | 0 | |
| Rv0340 | 0 | 1 | 0 | |
| iniB | 1 | 1 | 1.3 | 30 |
| iniA | 2 | 5 | 2.7 | >50 |
| iniC | 0 | 2 | 0 | |
| rmlD | 3 | 0 | 4.0 | >50 |
| wbbL | 0 | 0 | 0 | |
| rmlA2 | 0 | 1 | 0 | |
| Total | 38 | 43 | 50.7 | |
The MIC range shown is for the isolates with single-locus mutations. The MICs for isolates with multiple-locus mutations are shown in Table 4.
The four embA mutations were Ala462Val (n = 2) and Gly321Ser and Asp833Ala (n = 1 each). The embB mutations were Met306Val (n = 7), Met306Ile (n = 4), Gln497Arg (n = 3), Gly406Ala and Gly406Cys (n = 2 each), and Ser297Ala, Met306Leu, Asp328Gly, Phe330Val, Gly406Asp, Asp959Ala, Met1000Arg, and Asp1024Asn (n = 1 each). The two embR mutations were Gln379Arg and a change at position −137, an A insertion (n = 1 each). The iniB mutation was A47T. Two isolates had Ser501Trp changes in iniA. The rmlD changes were T284K (n = 1) and a change at position −71, G→T (n = 2). Nineteen isolates had EMB-resistance associated mutations in two or more genes.