Sequence Analyses of Just Four Genes To Detect Extensively Drug-Resistant Mycobacterium tuberculosis Strains in Multidrug-Resistant Tuberculosis Patients Undergoing Treatment
Sequence Analyses of Just Four Genes To Detect Extensively Drug-Resistant Mycobacterium tuberculosis Strains in Multidrug-Resistant Tuberculosis Patients Undergoing Treatment
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DOI：
10.1128/aac.00050-09
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发表时间：
2009-08-01
影响因子：
4.9
通讯作者：
Niemann, Stefan
中科院分区：
文献类型：
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作者：
Feuerriegel, Silke;Cox, Helen S.;Niemann, Stefan
对耐二线药物的结核分枝杆菌分离株进行快速检测，对于尽早制定适当的治疗方案至关重要。虽然分子方法已经成功地用于快速检测对一线药物的耐药性，但关于导致二线药物耐药性的突变的数据有限。为了解决这个问题，我们分析了来自乌兹别克斯坦的耐氧氟沙星(n=26)和卷曲霉素和/或阿米卡星(n=48)的结核分枝杆菌菌株的靶基因(gyrA、gyrB、rRs和tlyA)的变异。对照组为氧氟沙星敏感株(n=49)、卷曲霉素和/或阿米卡星敏感株(n=39)。96%(25/26)的氧氟沙星耐药菌株存在gyrA或gyrB基因突变，而敏感菌株均未发现这两个基因的突变。最常见的突变发生在GyrA基因第94位密码子(17/26株，65.4%)，其次是第90和91位密码子突变。两个菌株分别在密码子485和543处出现gyrB突变；这两个突变以前从未报道过。在同时对阿米卡星和卷曲霉素耐药的菌株中，最常见的突变是RRS中的A1401G(34/40株[85.0%])。有3株菌株的tlyA基因发生突变，其中2株(分别位于第18和118位密码子)与卷曲霉素耐药有关。总体而言，10株耐药株(5株阿米卡星耐药株和卷曲霉素敏感株)和39株敏感对照株中没有一株在所调查的基因中发生突变。我们的结果清楚地证明了相对较少的靶基因的短区域序列分析对于从接受多药耐药结核病治疗的患者分离的菌株中快速检测二线药物耐药性的潜力。在这种情况下，阿米卡星耐药的机制仍不清楚。
The rapid detection of Mycobacterium tuberculosis isolates resistant to second-line drugs is crucial for the institution of appropriate treatment regimens as early as possible. Although molecular methods have successfully been used for the rapid detection of resistance to first-line drugs, there are limited data on mutations that confer resistance to second-line drugs. To address this question, we analyzed Mycobacterium tuberculosis strains resistant to ofloxacin (n = 26) and to capreomycin and/or amikacin (n = 48) from Uzbekistan for variations in target genes (gyrA, gyrB, rrs, and tlyA). Strains susceptible to ofloxacin (n = 49) and capreomycin and/or amikacin (n = 39) were included as controls. Mutations in gyrA or gyrB were found in 96% (25/26 strains) of the ofloxacin-resistant strains, while none of the susceptible strains displayed mutations in those two genes. The most common mutation occurred in gyrA at codon 94 (17/26 strains [65.4%]), followed by mutations at codons 90 and 91. Two strains showed a mutation in gyrB, at codons 485 and 543, respectively; both mutations have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in rrs (34/40 strains [85.0%]). Three strains had mutations in tlyA, of which two (at codons 18 and 118) were associated with resistance to capreomycin alone. Overall, none of the 10 resistant strains (5 amikacin-resistant and capreomycin-susceptible strains) and none of the 39 susceptible control strains had mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions of relatively few target genes for the rapid detection of resistance to second-line drugs among strains isolated from patients undergoing treatment for multidrug-resistant tuberculosis. The mechanisms that confer amikacin resistance in this setting remain unclear.