Rapid Detection of Rifampicin-Resistance Mutations in Multidrug-Resistant Strains of Mycobacteriumtuberculosis in Morocco
Rapid Detection of Rifampicin-Resistance Mutations in Multidrug-Resistant Strains of Mycobacteriumtuberculosis in Morocco
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DOI：
10.1007/s100960100560
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发表时间：
2001-08
影响因子：
4.5
通讯作者：
Hafid Soualhine;M. Benlemlih;N. Oudghiri;D. Messaoudi;M. Timinouni
中科院分区：
文献类型：
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作者：
Hafid Soualhine;M. Benlemlih;N. Oudghiri;D. Messaoudi;M. Timinouni
597 don 526，代表将 His 替换为 Tyr 或 Asp。我们使用探针杂交鉴定出的突变中有 82% 影响密码子 531 和 526。这一发现与之前的研究结果一致 [4,5,6,7,10]，表明相同密码子的改变占所描述突变的 60%。我们的两个 MDR 分离株表现出易感特征，其中仅与野生型探针发生杂交。这一矛盾可能是由于 69 bp 高变区之外存在不确定突变或存在另一种耐药机制来解释的 [7, 8]。结核分枝杆菌的多药耐药性似乎是由基因编码药物靶标中个体突变事件的积累造成的。利福平耐药主要与 rpoB 基因 69 bp 区域的点突变有关，该基因编码 RNA 聚合酶 β 亚基 [4, 7]。这些基因改变导致 RNA 聚合酶的构象变化 [2]。使用市售的线性探针测定，我们在48小时内检测到利福平耐药性，并且测试结果与使用常规方法获得的结果相关。在我们的调查中，使用线性探针方法正确鉴定了 96% 的利福平耐药临床分离株。总之，线性探针测定被证明是一种快速检测结核分枝杆菌菌株利福平耐药性的方法。我们取得的结果表明，摩洛哥结核分枝杆菌利福平耐药临床分离株中最常见的突变涉及密码子 531 和 526。由于利福平耐药通常与异烟肼和链霉素耐药相关，因此快速检测利福平耐药可能有助于限制 MDR 菌株的传播，从而改善 MDR 结核病的管理。
597 don 526, representing a substitution of His to Tyr or Asp. Eighty-two percent of the mutations we identified using probe hybridization affected codons 531 and 526. This finding agrees with the results of previous studies [4, 5, 6, 7, 10], showing that alterations in the same codons account for up to 60% of mutations described. Two of our MDR isolates displayed a susceptible profile in which hybridization occurred with the wild-type probes only. This contradiction may be explained by the presence of an indeterminate mutation located outside of the 69 bp hypervariable region or by the existence of another mechanism of resistance [7, 8]. Multidrug resistance in Mycobacterium tuberculosis seems to result from an accumulation of individual mutational events in gene-encoding drug targets. Rifampicin resistance is mainly associated with point mutations located in the 69 bp region of the rpoB gene, which codes for the RNA polymerase β subunit [4, 7]. These genetic alterations lead to a conformational change of RNA polymerase [2]. Using a commercially available line probe assay, we detected rifampicin resistance within 48 h, and the test results correlated with those obtained using conventional methods. In our investigation, 96% of rifampicin-resistant clinical isolates were identified correctly with the line probe method. In conclusion, the line probe assay proved to be a rapid method for the detection of rifampicin resistance in Mycobacterium tuberculosis strains. The results we achieved demonstrate that the most frequently identified mutations in rifampicin-resistant clinical isolates of Mycobacterium tuberculosis in Morocco involve codons 531 and 526. Since resistance to rifampicin is often associated with resistance to isoniazid and streptomycin, rapid detection of rifampicin resistance may help limit the transmission of MDR strains in general, thereby improving the management of MDR tuberculosis.