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Volume 23, Number 3—March 2017

pncA Gene Mutations Associated with Pyrazinamide Resistance in Drug-Resistant Tuberculosis, South Africa and Georgia

Salim Allana, Elena Shashkina, Barun Mathema, Nino Bablishvili, Nestani Tukvadze, N. Sarita Shah, Russell R. Kempker, Henry M. Blumberg, Pravi Moodley, Koleka Mlisana, James C.M. Brust, and Neel R. GandhiComments to Author 
Author affiliations: Emory University Rollins School of Public Health and School of Medicine, Atlanta, Georgia, USA (S. Allana, R.R. Kempker, H.M. Blumberg, N.R. Gandhi); Rutgers University—Public Health Research Institute, Newark, New Jersey, USA (E. Shashkina); Columbia University Mailman School of Public Health, New York, New York, USA (B. Mathema); National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia (N. Bablishvili, N. Tukvadze); Centers for Disease Control and Prevention, Atlanta (N.S. Shah); University of KwaZulu-Natal and National Health Laboratory Service, Durban, South Africa (P. Moodley, K. Mlisana); Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA (J.C.M. Brust)

Main Article

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
3 AGG(R) 154 GGG(G) 17 (MDR TB: 3; XDR TB: 14) MDR 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
8 GGT(G) 132 GCT(A)§ 4 (MDR TB: 1; XDR TB: 3) MDR TB: HP
GGT(G) 97 GAT(D)§
2 (MDR TB: 1; XDR TB: 1)
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
Del T at 515§
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
Ins C after 456,
CTG(L) 35 CTA(L)¶
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.

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Page created: February 17, 2017
Page updated: February 17, 2017
Page reviewed: February 17, 2017
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