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Table 4 Evolution of drug resistance mutation sites of Mycobacterium tuberculosis to first-line anti tuberculosis drugs isoniazid and rifampin in 2014–2019

From: Prevalence and molecular characteristics of drug-resistant Mycobacterium tuberculosis in Hainan, China: from 2014 to 2019

Drug

Locus

Nucleic acid change

Codon mutation

2014 n (%)

2015 n (%)

2016 n (%)

2017 n (%)

2018 n (%)

2019 n (%)

Total

INH

KatG

AGC → AAC

Ser315Asn

4 (10.0)

0 (0.0) *

0 (0.0) *

1 (2.7)

3 (6.3)

5 (5.2)

13 (4.5)

  

AGC → ACC

Ser315Thr

30 (75.0)

5 (11.1)

10 (47.6)

34 (91.9)

40 (83.3)

72 (74.2)

191 (66.3)

 

inhA

C → T

C(−15) → T

0 (0.0)

0 (0.0)

1 (4.8)

2 (5.4)

5 (10.4)

15 (15.5) *

23 (8.0)

 

KatG + inhA

AGC → ACC + C → T

Ser315Thr + C(−15) → T

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

3 (3.1)

3 (1.0)

 

Other locus

Other mutations

Other substitutions

6 (15.0)

40 (88.9) *

10 (47.6) *

0 (0.0) *

0 (0.0) *

2 (2.1) *

58 (20.1)

Total

   

40 (100.0)

45 (100.0)

21 (100.0)

37 (100.0)

48 (100.0)

97 (100.0)

288 (100.0)

RIF

 

rpoB

CTG → CCG

Leu511Pro

8 (17.0)

1 (1.8) *

1 (2.6) *

3 (6.4)

4 (5.8)

10 (8.1)

27 (7.1)

  

CAA → CCA

Gln513Pro

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.8)

1 (0.3)

  

CAA → AAA

Gln513Lys

2 (4.3)

0 (0.0)

1 (2.6)

1 (2.1)

1 (1.5)

0 (0.0)

5 (1.3)

  

GAC → GGC

Asp516Gly

0 (0.0)

1 (1.8)

0 (0.0)

0 (0.0)

1 (1.5)

2 (1.6)

4 (1.0)

  

GAC → GTC

Asp516Val

4 (8.5)

1 (1.8)

0 (0.0)

2 (4.3)

2 (2.9)

3 (2.4)

12 (3.1)

  

GAC → TAC

Asp516Tyr

0 (0.0)

0 (0.0)

0 (0.0)

2 (4.3)

1 (1.5)

2 (1.6)

5 (1.3)

  

CAC → CGC

His526Arg

1 (2.1)

0 (0.0) *

1 (2.6)

1 (2.1)

4 (5.8)

1 (0.8)

8 (2.1)

  

CAC → CTC

His526Leu

1 (2.1)

0 (0.0)

1 (2.6)

1 (2.1)

3 (4.4)

1 (0.8)

7 (1.8)

  

CAC → GAC

His526Asp

4 (8.5)

1 (1.8)

0 (0.0)

4 (8.5)

4 (5.8)

10 (8.1)

23 (6.0)

  

CAC → TAC

His526Tyr

3 (6.4)

1 (1.8)

1 (2.6)

5 (10.6)

9 (13.0)

13 (10.5)

32 (8.4)

  

TCG → TGG

Ser531Trp

2 (4.3)

1 (1.8) *

0 (0.0)

1 (2.1) *

3 (4.4) *

1 (0.8) *

8 (2.1)

  

TCG → TTG

Ser531Leu

12 (25.5)

5 (8.8)

14 (35.9)

25 (53.2)

34 (49.3)

69 (55.6)

159 (41.5)

  

CTG → CCG

Leu533Pro

0 (0.0)

1 (1.8)

0 (0.0)

0 (0.0)

2 (2.9)

5 (4.0)

8 (2.1)

  

CTG → CCG+ GAC → GGC

Leu511Pro + Asp516Gly

1 (2.1)

0 (0.0)

0 (0.0)

1 (2.1)

0 (0.0)

0 (0.0)

2 (0.5)

  

CTG → CCG + GAC → TAC

Leu511Pro + Asp516Tyr

1 (2.1)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.3)

  

CTG → CCG + GAC → GTC

Leu511Pro + Asp516Val

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.8)

1 (0.3)

  

CTG → CCG + CAC → TAC

Leu511Pro + His526Tyr

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

2 (1.6)

2 (0.5)

  

CAA → CCA + GAC → GTC

Gln513Pro + Asp516Val

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.8)

1 (0.3)

  

GAC → GGC + CTG → CCG

Asp516Gly + Leu533Pro

2 (4.3)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.8)

3 (0.8)

 

Other locus

Other mutations

Other substitutions

6 (12.8)

45 (79.0) *

20 (51.3) *

1 (2.1)

1 (1.5) *

1 (0.8) *

74 (19.3)

Total

   

47 (100.0)

57 (100.0)

39 (100.0)

47 (100.0)

69 (100.0)

124 (100.0)

383 (100.0)

MDR

rpoB+ KatG

CTG → CCG+ AGC → ACC

Leu511Pro + Ser315Thr

8 (21.6)

0 (0.0) *

0 (0.0) *

0 (0.0) *

3 (7.0)

6 (8.1)

17 (7.0)

  

GAC → GGC + AGC → AAC

Asp516Gly + Ser315Asn

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (1.4)

1 (0.4)

  

GAC → GGC + AGC → ACC

Asp516Gly + Ser315Thr

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (1.4)

1 (0.4)

  

GAC → GTC + AGC → ACC

Asp516Val + Ser315Thr

3 (8.1)

0 (0.0)

0 (0.0)

1 (3.5)

2 (4.7)

1 (1.4)

7 (2.9)

  

GAC → TAC + AGC → ACC

Asp516Tyr + Ser315Thr

0 (0.0)

0 (0.0)

0 (0.0)

1 (3.5)

1 (2.3)

1 (1.4)

3 (1.2)

  

CAC → CGC + AGC → ACC

His526Arg + Ser315Thr

1 (2.7)

0 (0.0) *

1 (5.0)

1 (3.5)

3 (7.0)

0 (0.0)

6 (2.5)

  

CAC → CTC + AGC → ACC

His526Leu + Ser315Thr

1 (2.7)

0 (0.0)

0 (0.0)

1 (3.5)

0 (0.0)

0 (0.0)

2 (0.8)

  

CAC → GAC + AGC → AAC

His526Asp + Ser315Asn

1 (2.7)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.4)

  

CAC → GAC + AGC → ACC

His526Asp + Ser315Thr

3 (8.1)

1 (2.6)

0 (0.0)

3 (10.3)

3 (7.0)

5 (6.8)

15 (6.2)

  

CAC → TAC + AGC → ACC

His526Tyr + Ser315Thr

1 (2.7)

0 (0.0)

1 (5.0)

5 (17.2)

5 (11.6)

7 (9.5)

19 (7.9)

  

TCG → TGG + AGC → AAC

Ser531Trp + Ser315Asn

0 (0.0)

0 (0.0) *

0 (0.0)

0 (0.0)

1 (2.3) *

0 (0.0) *

1 (0.4)

  

TCG → TGG + AGC → ACC

Ser531Trp + Ser315Thr

2 (5.4)

1 (2.6)

0 (0.0)

0 (0.0)

1 (2.3)

1 (1.4)

5 (2.1)

  

TCG → TTG + AGC → AAC

Ser531Leu + Ser315Asn

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

2 (4.7)

4 (5.4)

6 (2.5)

  

TCG → TTG + AGC → ACC

Ser531Leu + Ser315Thr

8 (21.6)

2 (5.1)

8 (40.0)

14 (48.3)

18 (41.9)

34 (46.0)

84 (34.7)

  

CTG → CCG + AGC → ACC

Leu533Pro + Ser315Thr

0 (0.0)

1 (2.6)

0 (0.0)

0 (0.0)

0 (0.0)

3 (4.1)

4 (1.7)

 

rpoB + inhA

GAC → GGC + C → T

Asp516Gly + C(−15) → T

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (2.3)

0 (0.0)

1 (0.4)

  

CAC → CGC + C → T

His526Arg + C(−15) → T

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (2.3)

0 (0.0)

1 (0.4)

  

TCG → TGG + C → T

Ser531Trp + C(−15) → T

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (2.3)

0 (0.0)

1 (0.4)

  

TCG → TTG + C → T

Ser531Leu + C(−15) → T

0 (0.0)

0 (0.0)

1 (5.0)

2 (6.9)

1 (2.3)

1 (1.4)

5 (2.1)

 

rpoB + rpoB + KatG

CTG → CCG + GAC → GGC + AGC → ACC

Leu511Pro + Asp516Gly + Ser315Thr

1 (2.7)

0 (0.0)

0 (0.0)

1 (3.5)

0 (0.0)

0 (0.0)

2 (0.8)

  

CTG → CCG + GAC → GTC + AGC → ACC

Leu511Pro + Asp516Val + Ser315Thr

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (1.4)

1 (0.4)

  

CTG → CCG + CAC → TAC + AGC → ACC

Leu511Pro + His526Tyr + Ser315Thr

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (1.4)

1 (0.4)

  

CAA → CCA + GAC → GTC + AGC → ACC

Gln513Pro + Asp516Val + Ser315Thr

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (1.4)

1 (0.4)

  

GAC → GGC + CTG → CCG + AGC → AAC

Asp516Gly + Leu533Pro + Ser315Asn

2 (5.4)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

2 (0.8)

  

GAC → GGC + CTG → CCG + AGC → ACC

Asp516Gly + Leu533Pro + Ser315Thr

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (1.4)

1 (0.4)

 

rpoB + KatG + inhA

TCG → TTG + AGC → ACC + C → T

Ser531Leu + Ser315Thr + C(−15) → T

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

3 (4.1)

3 (1.2)

 

Other locus

Other mutations

Other substitutions

6 (16.2)

34 (87.2) *

9 (45.0) *

0 (0.0) *

0 (0.0) *

2 (2.8) *

51 (21.1)

 

Total

  

37 (100.0)

39 (100.0)

20 (100.0)

29 (100.0)

43 (100.0)

74 (100.0)

242 (100.0)

  1. Note: * indicates that the difference is statistically significant compared with 2014