Table 1.
Mutations detected in all strains analyzed
| Gene | Mutation | Strains phenotypically susceptible to INH (n=) | Strains phenotypically resistant to INH (n=) |
|---|---|---|---|
|
katG |
wild type |
65 |
4(1) |
| |
Ala291Thr (gct/act); Ser315Thr (agc/acc) |
|
1 |
| |
Trp300Cys (tgg/tgc) |
|
1 |
| |
Thr302Arg (acg/agg) |
|
1 |
| |
Ser315Thr (acg/acc) |
|
21 |
| |
Asp329 (gac/ggac frameshift) |
|
1 |
| |
Arg463Leu (cgg/ctg)(2) |
|
2 |
| |
Gln471Arg (cag/cgg); Ser315Thr (agc/acc) |
|
1 |
| |
Strains phenotypically susceptible to RIF (n=) |
Strains phenotypically resistant to RIF (n=) |
|
|
rpoB |
wild type |
76 |
|
| |
Thr481Ala (acc/gcc)(3) |
|
1 |
| |
Leu511Pro (ctg/ccg)(4) |
1 |
|
| |
Asp516Tyr (gac/tac)(4) |
3 |
|
| |
His526Tyr (cac/tac) |
|
3 |
| |
His526Arg (cac/cgc) |
|
3 |
| |
Ser531Leu (tcg/ttg) |
|
8 |
| |
Leu533Pro (ctg/ccg)(4) |
1 |
1 |
| |
Strains phenotypically susceptible to SM (n=) |
Strains phenotypically resistant to SM (n=) |
|
|
rpsL |
wild type |
56 |
21 |
| |
Lys43Arg (aag/agg) |
|
11 |
| |
Lys88Arg (aag/agg) |
1 |
8 |
|
gidB |
wild type |
26 (2 with mutations in rrs/rpsL) |
15 (10 with mutations in rpsL) |
| |
Leu16Arg (ctt/cgt) |
4 |
2 |
| |
Leu16Arg (ctt/cgt); Gln127stop (caa/taa); Ala161Ala (gcc/gcg) |
1 |
|
| |
Leu16Arg (ctt/cgt); Ala161Ala (gcc/gcg) |
2 |
1 (Lys43Arg in rpsL) |
| |
Leu16Arg (ctt/cgt); Ala200Glu (gcg/gag) |
|
2 |
| |
Leu16Arg (ctt/cgt); Ala205Ala (gca/gcg) |
|
1 (Lys43Arg in rpsL) |
| |
Gly34Ala (ggg/gcg) |
|
1 |
| |
Pro38 (ccc/cc frameshift) |
|
1 (Lys88Arg in rpsL) |
| |
Val65Gly (gtc/ggc) |
|
1 |
| |
Gly69Asp (ggt/gat) |
1 |
2 |
| |
Gly71Arg (gga/aga) |
|
1 |
| |
Val88Ala (gta/gca) |
|
1 |
| |
Leu91Pro (cta/cca) |
|
1 |
| |
Gly92Asp (gaa/gac) |
1 |
|
| |
Gly92Asp (gaa/gac); Ala205Ala (gca/gcg) |
|
3 (Lys43Arg in rpsL) |
| |
Ser100Phe (tct/ttt) |
|
1 |
| |
Val110Val (gtg/gtt); Ala205Ala (gca/gcg) |
4 |
|
| |
Ala138Val (gcg/gtg) |
|
2 |
| |
Ala200Glu (gcg/gag) + Ala205Ala (gca/gcg) |
|
1 |
| |
Ala205Ala (gca/gcg) |
18 |
4 (3 with mutations in rpsL) |
| |
Strains phenotypically susceptible to EMB (n=) |
Strains phenotypically resistant to EMB (n=) |
|
|
embB |
wild type |
82 |
4(5) |
| |
Met306Ile (atg/ata) |
|
6 |
| |
Met306Val (atg/gtg) |
|
1 |
| |
Trp332Arg (tgg/cgg) |
|
1 |
| |
Gln497Lys (cag/aag)(3) |
|
1 |
| |
Gln1002Arg (cag/cgc)(3) |
|
2 |
| |
Strains phenotypically susceptible to PZA (n=) |
Strains phenotypically resistant to PZA (n=) |
|
|
pncA |
wild type |
84 |
3 |
| |
−11 (a/g) |
|
1 |
| |
Ile5 (atc/atcc frameshift) |
|
1 |
| |
Thr47Ala (acc/gcc) |
2 |
|
| |
Tyr64 (tat/tata frameshift) |
|
1 |
| |
Lys96Glu (aag/gag) |
1 |
|
| |
Gln141 (cag/cag acggcgccag (insertion of 10 bp → frameshift) |
|
1 |
| |
Ala146Glu (gcg/gag) |
|
1 |
| |
Gly162Asp (ggt/gat) |
|
1 |
| Leu172Pro (ctg/ccg) | 1 | ||
Sequence analysis and drug susceptibility testing has been repeated for all strains showing discrepant results.
Abbreviations: INH, isoniazid; RIF, rifampin; SM, streptomycin; EMB, ethambutol; PZA, pyrazinamide.
(1)Those strains were additionally sequenced in the promoter region of inhA and ahpC. Two of them carried a mutation in inhA at position −15 (C → T) and one in ahpC at −57 (C → T).
(2)Arg463Leu is a phylogenetic SNP [23] and was excluded for further analysis.
(3)These mutations were identified by sequence analysis of the complete gene.
(4)These mutations confer low-level RIF resistance.
(5)These strains were sequenced in the complete embCAB operon. One strain carried a mutation in embC [Val981Leu (gtg/ctg)].