分析来自埃塞俄比亚的结核分枝杆菌分离株中与异烟肼、利福平及乙胺丁醇耐药相关的基因突变。
Analysis of gene mutations associated with isoniazid, rifampicin and ethambutol resistance among Mycobacterium tuberculosis isolates from Ethiopia.
机构信息
Department of Medical Laboratory Technology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
出版信息
BMC Infect Dis. 2012 Feb 10;12:37. doi: 10.1186/1471-2334-12-37.
BACKGROUND
The emergence of drug resistance is one of the most important threats to tuberculosis control programs. This study was aimed to analyze the frequency of gene mutations associated with resistance to isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) among Mycobacterium tuberculosis isolates from Northwest Ethiopia, and to assess the performance of the GenoType® MTBDRplus and GenoType® MTBDRsl assays as compared to the BacT/ALERT 3D system.
METHODS
Two hundred sixty Mycobacterium tuberculosis isolates from smear positive tuberculosis patients diagnosed between March 2009 and July 2009 were included in this study. Drug susceptibility tests were performed in the Institute of Medical Microbiology and Epidemiology of Infectious Diseases, University Hospital of Leipzig, Germany.
RESULTS
Of 260 isolates, mutations conferring resistance to INH, RMP, or EMB were detected in 35, 15, and 8 isolates, respectively, while multidrug resistance (MDR) was present in 13 of the isolates. Of 35 INH resistant strains, 33 had mutations in the katG gene at Ser315Thr 1 and two strains had mutation in the inhA gene at C15T. Among 15 RMP resistant isolates, 11 had rpoB gene mutation at Ser531Leu, one at His526Asp, and three strains had mutations only at the wild type probes. Of 8 EMB resistant strains, two had mutations in the embB gene at Met306Ile, one at Met306Val, and five strains had mutations only at the wild type probes. The GenoType® MTBDRplus assay had a sensitivity of 92% and specificity of 99% for INH resistance, and 100% sensitivity and specificity to detect RMP resistance and MDR. The GenoType® MTBDRsl assay had a sensitivity of 42% and specificity of 100% for EMB resistance.
CONCLUSION
The dominance of single gene mutations associated with the resistance to INH and RMP was observed in the codon 315 of the katG gene and codon 531 of the rpoB gene, respectively. The GenoType® MTBDRplus assay is a sensitive and specific tool for diagnosis of resistance to INH, RMP and MDR. However, the GenoType® MTBDRsl assay shows limitations in detecting resistance to EMB.
背景
耐药性的出现是结核病控制规划面临的最重要威胁之一。本研究旨在分析来自埃塞俄比亚西北部的结核分枝杆菌分离株中与异烟肼（INH）、利福平（RMP）和乙胺丁醇（EMB）耐药相关的基因突变频率，并评估 GenoType® MTBDRplus 和 GenoType® MTBDRsl 检测与 BacT/ALERT 3D 系统相比的性能。
方法
本研究纳入了 2009 年 3 月至 2009 年 7 月期间在德国莱比锡大学医院医学微生物学和传染病流行病学研究所诊断为涂片阳性的肺结核患者的 260 株结核分枝杆菌分离株。药敏试验在德国莱比锡大学医院医学微生物学和传染病流行病学研究所进行。
结果
在 260 株分离株中，35 株、15 株和 8 株分别检测到对 INH、RMP 和 EMB 的耐药性相关突变，而 13 株分离株存在耐多药（MDR）。35 株 INH 耐药株中，33 株 katG 基因 Ser315Thr 1 发生突变，2 株 inhA 基因 C15T 发生突变。15 株 RMP 耐药株中，11 株 rpoB 基因 Ser531Leu 发生突变，1 株 His526Asp 发生突变，3 株仅在野生型探针处发生突变。8 株 EMB 耐药株中，2 株 embB 基因 Met306Ile 发生突变，1 株 Met306Val 发生突变，5 株仅在野生型探针处发生突变。GenoType® MTBDRplus 检测对 INH 耐药的敏感性为 92%，特异性为 99%，对检测 RMP 耐药和 MDR 的敏感性和特异性均为 100%。GenoType® MTBDRsl 检测对 EMB 耐药的敏感性为 42%，特异性为 100%。
结论
在 katG 基因的 315 密码子和 rpoB 基因的 531 密码子中分别观察到与 INH 和 RMP 耐药相关的单个基因突变的主导地位。GenoType® MTBDRplus 检测是一种敏感且特异的 INH、RMP 和 MDR 耐药诊断工具。然而，GenoType® MTBDRsl 检测在检测 EMB 耐药方面存在局限性。
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