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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