TABLE 3.
pncA mutation profilea
Nucleotide change | Amino acid change(s) | SNP location(s) | No. of cases | M. tuberculosis lineage(s)b | MGIT PZA susceptibility assay resultb,c |
---|---|---|---|---|---|
Single mutation | |||||
(−4) ins Cd | NA | Promoter | 1 | EAI5 | S |
149 ins Td | Frameshift at Cd50 | 149 | 1 | Beijing | S |
156 ins Td | Frameshift at Cd53 | 156 | 1 | Beijing | R |
159 ins Ad | Frameshift at Cd54 | 159 | 1 | T1 | S |
166 ins Gd | Frameshift at Cd56 | 166 | 1 | Beijing | S |
391 ins GG | Frameshift at Cd131 | 391 | 1 | Beijing | R |
392 ins GG | Frameshift at Cd131 | 392 | 1 | EAI1-SOM | R |
445 ins GCd | Frameshift at Cd149 | 445 | 6 | LAM9 (6) | R (6) |
450 ins GCd | Frameshift at Cd150 | 450 | 1 | Beijing | R |
518 ins Gd | Frameshift at Cd173 | 518 | 1 | Beijing | R |
del 558 Gd | Frameshift at Cd186 | 558 | 1 | EAI | R |
A(−11)G | NA | Promoter | 2 | Beijing (1), CAS1-Delhi (1) | R, R |
A(−15)C | NA | Promoter | 3 | T1 (2), Orphan (1) | S, S, R |
AAG to ATG | Lys96Met | 287 | 1 | LAM9 | R |
AAT to AGTd | Asn149Ser | 446 | 1 | T1 | S |
ACC to CCC | Thr47Pro | 139 | 2 | Beijing | R (2) |
ACT to CCT | Thr76Pro | 226 | 1 | EAI1-SOM | R |
AGC to AGG | Ser104Arg | 312 | 2 | Beijing (2) | R, S |
ATT to ACT | Ile133Thr | 398 | 1 | Orphan | R |
CAA to TAA | Gln122Stop | 364 | 1 | Beijing | S |
CAC to CAG | His51Gln | 153 | 1 | T1 | R |
CAC to CCC | His51Pro | 152 | 1 | Beijing | R |
CAG to AAG | Gln10Lys | 28 | 1 | LAM10-CAM | R |
CAG to TAG | Gln10Stop | 28 | 1 | EAI1-SOM | R |
CAT to CCT | His137Pro | 410 | 1 | T1 | R |
CAT to CGT | His71Arg | 212 | 1 | Beijing | R |
CAT to CTTd | His137Leu | 410 | 1 | T1 | R |
CCG to TCG | Pro54Ser | 160 | 1 | Orphan | S |
CCG to CTG | Pro54Leu | 160 | 1 | Orphan | R |
CTG to CCG | Leu172Pro | 515 | 1 | T1 | R |
CGG to TGGd | Arg2Trp | 4 | 1 | LAM9 | S |
del 340 Ad | Frameshift at Cd114 | 340 | 1 | Beijing | R |
del 112 to 561d | del of Cd37 to Cd187 | 112–561 | 3 | Beijing (3) | R (3) |
del 296 to 309d | Frameshift at Cd99 | 296–309 | 1 | T1 | R |
GAC to AAC | Asp49Asn | 145 | 1 | Beijing | R |
GAC to GCC | Asp12Ala | 35 | 1 | LAM9 | R |
GCC to ACCd | Ala28Thr | 82 | 1 | EAI3-IND | S |
GCG to ACG | Ala171Thr | 511 | 1 | Beijing | R |
GCG to GTG | Ala171Val | 512 | 1 | T1 | S |
GCG to GGGd | Ala171Gly | 512 | 1 | T1 | S |
GGC to GACd | Gly105Asp | 314 | 3 | T1 (3) | R (2), S (1) |
GGC to GAC | Gly24Asp | 71 | 1 | Beijing | R |
GTG to GCG | Val139Ala | 416 | 1 | T1 | R |
GTG to ATGd | Val155Met | 463 | 1 | EAI-SOM | R |
TAC to CAC | Tyr103His | 307 | 1 | T1 | S |
TAC to TAA | Tyr95Stop | 285 | 1 | T1 | R |
TAC to TAG | Tyr99Stop | 297 | 3 | Beijing | R (2), S (1) |
TAC to TGC | Tyr103Arg | 308 | 1 | Orphan | R |
TCC to TCT | Ser65Ser | 195 | 10 | CAS1-Delhi (10) | S (8), R (2) |
TGT to GGTd | Cys138Gly | 412 | 1 | Orphan | R |
TTC to GTCd | Phe58Val | 172 | 1 | Beijing | S |
TTG to TGG | Leu4Trp | 12 | 2 | CAS1-Delhi (2) | R (2) |
Multiple mutations | |||||
TCC to TCT, 295 ins C,d 430 ins C,d 467 ins Cd | Ser65Ser and frameshift at Cd99,144,156 | 195, 295, 430, 467 | 1 | CAS1-Delhi | S |
AAG to GAG, AGG to ACG, GAG to CAGd | Lys96Glu, Arg154Thr, Glu181Gln | 286, 461, 541 | 1 | EAI5 | R |
TCC to TCT, ACT to ATT | Ser65Ser, Thr76Ile | 195, 227 | 1 | CAS2 | R |
TGG to TGA, 445 ins GC | Trp119Stop, frameshift at Cd149 | 357, 445 | 1 | LAM9 | R |
GAC to GCC, 178 ins Cd | Asp12Ala, frameshift at Cd60 | 35, 178 | 1 | LAM9 | S |
A(−15)C, TCG to CCG | NA, Ser67Pro | Promoter, 199 | 1 | T1 | R |
GCG to GGG,d GGC to GAC | Ala38Gly, Gly105Asp | 113, 314 | 1 | T1 | R |
TCC to TCT, GGT to AGT | Ser65Ser, Gly97Ser | 195, 289 | 1 | CAS1-Delhi | R |
TAC to TGC, TGG to CGG | Tyr34Cys, Trp68Arg | 101, 202 | 1 | LAM9 | S |
SNP, single nucleotide polymorphism; R, resistant; S, sensitive/susceptible; ins, insertion; del, deletion; NA, not applicable; nt, nucleotide; Cd, codon.
Numbers in parentheses indicate the number of isolates of that type.
Results of the MGIT assay for PZA susceptibility separated by a comma indicate the corresponding result for the M. tuberculosis lineage.
New mutation.