Whole-genome sequence analysis and comparisons between drug-resistance mutations and minimum inhibitory concentrations of Mycobacterium tuberculosis isolates causing M/XDR-TB

被引：27

作者：

Nonghanphithak, Ditthawat ^{[1
,2
]}

Kaewprasert, Orawee ^{[1
,2
]}

Chaiyachat, Pratchakan ^{[1
,2
]}

Reechaipichitkul, Wipa ^{[2
,3
]}

Chaiprasert, Angkana ^{[4
]}

Faksri, Kiatichai ^{[1
,2
]}

机构：

[1] Khon Kaen Univ, Fac Med, Dept Microbiol, Khon Kaen, Thailand

[2] Khon Kaen Univ, Res & Diagnost Ctr Emerging Infect Dis RCEID, Khon Kaen, Thailand

[3] Khon Kaen Univ, Fac Med, Dept Med, Khon Kaen, Thailand

[4] Mahidol Univ, Siriraj Hosp, Fac Med, Drug Resistant TB Res Fund Lab,Res & Dev Affairs, Bangkok, Thailand

来源：

PLOS ONE | 2020年 / 15卷 / 12期

关键词：

ANTIBIOTIC-RESISTANCE; SUSCEPTIBILITY; EVOLUTION; RIFAMPIN;

D O I：

10.1371/journal.pone.0244829

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Drug resistance (DR) remains a major challenge for tuberculosis (TB) control. Whole-genome sequencing (WGS) provides the highest genetic resolution for genotypic drug-susceptibility tests (DST). We compared DST profiles of 60 Mycobacterium tuberculosis isolates which were drug resistant according to agar proportion tests (one poly DR-TB, 34 multidrug-resistant TB and 25 extensively drug-resistant TB). We additionally performed minimum inhibitory concentration (MIC) tests using Sensititre MYCOTBI plates (MYCOTB) and a WGS-based DST. Agreement between WGS-based DST and MYCOTB was high for all drugs except ethambutol (65%) and ethionamide (62%). Isolates harboring the -15 c/t inhA promoter mutation had a significantly lower MIC for isoniazid than did isolates with the katG Ser315Thr mutation (p < 0.001). Similar patterns were seen for ethambutol (embB Gly406Asp vs. embB Met306Ile), streptomycin (gid Gly73Ala vs. rpsL Lys43Arg), moxifloxacin (gyrA Ala90Val vs. gyrA Asp94Gly) and rifabutin (rpoB Asp435Phe/Tyr/Val vs. rpoB Ser450Leu). For genotypic heteroresistance, isolates with lower proportion of mapped read tended to has lower MIC of anti-TB drugs than those with higher proportion. These results emphasize the high applicability of WGS for determination of DR-TB and the association of particular mutations with MIC levels.

引用

页数：14

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