Table 1. pncA gene sequencing and RFLP results of 74 MDR TB and 377 XDR TB isolates from KwaZulu-Natal Province, South Africa*.
| Mutation | pncA mutation type† | Frequency (no. isolates) | RFLP‡ |
|---|---|---|---|
| Mutations common to MDR TB and XDR TB isolates | |||
| 1 | Ins C after 456 | 271 (MDR TB: 7; XDR TB: 264) | MDR TB: HP |
| XDR TB: HP (263), mixed (1) | |||
| 2 | TTG(L) 151 TCG(S)§ | 19 (MDR TB: 8; XDR TB: 11) | MDR TB: GY |
| XDR TB: GY | |||
| 3 | AGG(R) 154 GGG(G) | 17 (MDR TB: 3; XDR TB: 14) | MDR TB: AH |
| XDR TB: AH | |||
| 4 | GCG(A) 102 GTG(V)§ | 15 (MDR TB: 13; XDR TB: 2) | MDR TB: BW (1), KO (12) |
| XDR TB: BM (1), KO (1) | |||
| 5 | CAT(H) 71 TAT(Y)§ | 13 (MDR TB: 3; XDR TB: 10) | MDR TB: BH (1), BW (2) |
| XDR TB: BH (1), BW (8), HP (1) | |||
| 6 | Ins A after 408§ | 8 (MDR TB: 1; XDR TB: 7) | MDR TB: CC |
| XDR TB: CC (6), GY (1) | |||
| 7 | TCC(S) 59 CCC(P)§ | 7 (MDR TB: 4; XDR TB: 3) | MDR TB: BF |
| XDR TB: BF | |||
| 8 | GGT(G) 132 GCT(A)§ | 4 (MDR TB: 1; XDR TB: 3) | MDR TB: HP |
| XDR TB: HP | |||
| 9 |
GGT(G) 97 GAT(D)§ |
2 (MDR TB: 1; XDR TB: 1) |
MDR TB: KM |
| XDR TB: M | |||
| Mutations specific to MDR TB isolates | |||
| 10 | CTG(L) 35 CTA(L)¶ | 1 | W |
| 11 | CTG(L) 35 CTA(L)¶ | 1 | GY |
| TTG(L) 151 TCG(S) | |||
| 12 | TTC(F) 58 TCC(S)§ | 1 | BH |
| 13 | ACT(T) 76 ATT(I)§ | 1 | CC |
| 14 | GAG(E) 91 CAG(Q) | 1 | BH |
| 15 | GGT(G) 97 TGT(C)§ | 1 | H |
| 16 | Ins A after 407§ | 1 | CC |
| 17 | Del CAGGGTGC at 459 | 1 | W |
| 18 |
Del T at 515§ |
1 |
GO |
| Mutations specific to XDR TB isolates | |||
| 19 | insG after 515 | 23 | MH |
| 20 | TAC(Y) 34 GAC(D)§ | 5 | BH |
| 21 | GTG(V) 139 GGG(G)§ | 3 | HP |
| 22 | GTG(V) 130 GCG(A)# | 2 | W |
| 23 | Del G at 385, TTG(L) 151 TCG(S) | 2 | GY |
| 24 | GAG(E) 15 GGG(G) | 1 | W |
| 25 | ACC(T) 47 ATC(I) | 1 | KR |
| 26 | CAC(H) 51 CCC(P) § | 1 | HP |
| 27 | TCC(S) 65 TCT(S)¶,# | 1 | GD |
| 28 | TGC(C) 104 CGC(R) | 1 | MH |
| 29 | ACC(T) 153 CAC(H)§ | 1 | HP |
| 30 | AGG(R) 154 TGG(W)§ | 1 | HP |
| 31 | Ins G after 312 | 1 | HP |
| 32 | Ins G after 313 | 1 | HP |
| 33 | Del T at 389 | 1 | HP |
| 34 |
Ins C after 456,
CTG(L) 35 CTA(L)¶ |
1 |
HP |
| Wild-type | 40 (MDR TB: 24; XDR TB: 16) | MDR TB: BE (2), BH (4), BM (1), BW (1), CC (2), FO (1), GO (1), GY (1), HZ (1), MH (2), W (8); XDR TB: AH (1), BM (1), BW (1), CC (1), GY (1), HP (2), MH (4), mixed (1), W (4) | |
*del, deletion; ins, insertion; MDR, multidrug resistant; RFLP, restriction fragment-length polymorphism; SNP, single-nucleotide polymorphism; TB, tuberculosis; XDR, extensively drug-resistant. Row colors: pink, frameshift mutations (insertions or deletions); green, synonymous mutations or SNPs reported as being associated with phenotypic susceptibility to pyrazinamide; gray, SNPs reported as being associated with phenotypic resistance to pyrazinamide; blue, single-nucleotide polymorphisms not previously reported in the literature. †Insertions and deletions are presented with the nucleotide position where the polymorphism occurred; SNPs are presented with the codon position and the original and mutated 3 nucleotides and amino acid. ‡The nomenclature used for classifying IS6110 RFLP patterns was as follows: 2 isolates with an identical IS6110 banding pattern were assigned the same arbitrary 1- or 2-letter code (e.g., W, HP, or AB), which started with the first observed cluster, strain A (several decades ago). IS6110 patterns that were similar but not identical were denoted by the addition of a number (e.g., BE1, W4, or HP81). This table shows only the letter designations; numbers have been omitted for simplicity. Strains within each of the 2-letter designations had similar RFLP patterns. §Reported in the literature as being associated with resistance to pyrazinamide. ¶Synonymous mutation. #Reported in the literature as being associated with susceptibility to pyrazinamide.