在埃塞俄比亚的淋巴结抽吸物中分离的结核分枝杆菌分离株中，导致耐药性的基因突变程度。
Magnitude of gene mutations conferring drug resistance in mycobacterium tuberculosis isolates from lymph node aspirates in ethiopia.
机构信息
1. College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia; ; 2. Institute of Medical Microbiology and Epidemiology of Infectious Diseases, University Hospital, University of Leipzig, Leipzig, Germany; ; 3. Institute of Clinical Immunology, University Hospital, University of Leipzig, Leipzig, Germany; ; 5. Translational Centre for Regenerative Medicine (TRM)-Leipzig, University Hospital, University of Leipzig, Leipzig, Germany.
出版信息
Int J Med Sci. 2013 Sep 12;10(11):1589-94. doi: 10.7150/ijms.6806. eCollection 2013.
OBJECTIVE
Resistance to drugs is due to particular genomic mutations in the specific genes of Mycobacterium tuberculosis. Timely genetic characterization will allow identification of resistance mutations that will optimize an effective antibiotic treatment regimen. We determine the magnitude of gene mutations conferring resistance to isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) among tuberculosis (TB) lymphadenitis patients.
METHODS
A cross sectional prospective study was conducted among 226 M.tuberculosis isolates from culture positive lymph node aspirates collected from TB lymphadenitis patients between April 2012 and May 2012. Detection of mutations conferring resistance to drugs was carried out using GenoType(®) MTBDRplus and GenoType® MTBDRsl assay.
RESULTS
Out of the 226 strains, mutations conferring resistance to INH, RMP, multidrug resistance tuberculosis (MDR-TB) and EMB were 8, 3, 2 and 2 isolates, respectively. There was no isolated strain that showed mutation in the inhA promoter region gene. All INH resistant strains had mutations in the katG gene at codon 315 with amino acid change of S315T1. Among rifampicin resistant strains, two isolates displayed mutations at codon 531 in the rpoB gene with amino acid change of S531L and one isolate was by omission of wild type probes at Q513L. According to mutations associated with ethambutol resistance, all of the isolates had mutations in the embB gene with aminoacid change of M306I. All isolates resistant to INH, RMP and MDR using BacT/AlerT 3D system were correctly identified by GenoType® MTBDRplus assay.
CONCLUSION
We observed mutations conferring resistance to INH at S315T1 of the katG gene, RMP at S531L and Q513L in the rpoB genes and EMB at M306I of the embB gene. In the absence of conventional drug susceptibility testing, the effort to develop easy, rapid and cost effective molecular assays for drug resistance TB monitoring is definitely desirable and the GenoType® MTBDRplus assay was found to be a useful method for diagnosis of resistance to INH, RMP and MDR from lymph node aspirates. Further molecular cluster analysis to determine transmission dynamics of mutated strain is required.
目的
耐药性是由于结核分枝杆菌特定基因中的特定基因组突变引起的。及时进行基因特征分析将有助于确定耐药突变，从而优化有效的抗生素治疗方案。本研究旨在确定结核性淋巴结炎患者中异烟肼（INH）、利福平（RMP）和乙胺丁醇（EMB）耐药相关基因突变的发生率。
方法
2012 年 4 月至 5 月期间，对结核性淋巴结炎患者的淋巴结抽吸物培养阳性的 226 株结核分枝杆菌进行了一项横断面前瞻性研究。采用 GenoType® MTBDRplus 和 GenoType® MTBDRsl 检测药物耐药相关突变。
结果
226 株菌株中，对 INH、RMP、耐多药结核（MDR-TB）和 EMB 耐药的突变分别为 8、3、2 和 2 株。没有一株菌株存在 inhA 启动子区域基因的突变。所有 INH 耐药株的 katG 基因均在 315 密码子处发生突变，导致 S315T1 氨基酸改变。利福平耐药株中，2 株在 rpoB 基因的 531 密码子处发生突变，导致 S531L 氨基酸改变，1 株在 Q513L 处野生型探针缺失。根据与乙胺丁醇耐药相关的突变，所有菌株在 embB 基因均发生 M306I 氨基酸改变。BacT/AlerT 3D 系统检测到的 INH、RMP 和 MDR 耐药的所有菌株均被 GenoType® MTBDRplus 检测正确识别。
结论
本研究观察到 INH 耐药相关突变位于 katG 基因的 S315T1、rpoB 基因的 S531L 和 Q513L 以及 embB 基因的 M306I。在缺乏常规药敏检测的情况下，开发简单、快速、经济有效的耐药结核监测分子检测方法是非常必要的，GenoType® MTBDRplus 检测方法被证明是一种用于诊断淋巴结抽吸物中 INH、RMP 和 MDR 耐药的有用方法。还需要进一步进行分子聚类分析，以确定突变株的传播动力学。
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