Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates
Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates
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DOI：
10.1128/jcm.39.1.107-110.2001
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发表时间：
2001-01-01
影响因子：
9.4
通讯作者：
Niemann, S
中科院分区：
文献类型：
--
作者：
Heep, M;Brandstätter, B;Niemann, S
通过分析1997年在德国分离的80株利福平（RIF）耐药结核分枝杆菌菌株中rpoB突变的分布，确定了最近描述的突变V176 F（位于rpoB基因的起始处，与利福平耐药和野生型簇I序列相关）的患病率。最常见的rpoB突变是密码子456（52株，65%）的变化，其次是密码子441（13株，16%）和密码子451（11株，14%）的变化。V176 F突变在研究人群的一个分离株中检测到，在6项先前发表的研究中，18个RIF耐药菌株中有5个没有簇I突变。在三个分离物中，（异源抗性）在初始分析中禁止检测rpoB突变;然而，在这些分离株中，在含RIF的培养基上传代后，可以验证簇I突变，76株菌株的IS 6110 DNA指纹图谱显示8个聚类，包括27株具有相同限制性片段长度多态性模式的菌株，相同的rpoB突变和相同或相似的耐药模式。总之，我们的研究结果表明，V176 F突变应包括在分子检测预测RIF耐药的M。结核我们进一步证明了由对RIF具有不同亲和性的分枝杆菌亚群的混合物引起的异源耐药性可能影响用于检测耐药性的分子测试的灵敏度。
The prevalence of recently described mutation V176F, located in the beginning of the rpoB gene and associated with rifampin resistance and the wild-type cluster I sequence, was determined by analyzing the distribution of rpoB mutations among 80 rifampin (RIF)-resistant Mycobacterium tuberculosis strains isolated in Germany during 1997. The most frequent rpoB mutations were changes in codon 456 (52 isolates, 65%), followed by changes in codon 441 (13 isolates, 16%) and codon 451 (11 isolates, 14%). The V176F mutation was detected in one isolate of the study population and in 5 of 18 RIF-resistant strains with no cluster I mutation from six previously published studies. In three isolates, a mixture of resistant and susceptible subpopulations (heteroresistance) prohibited the detection of rpoB mutations in the initial analysis; however, in these isolates, cluster I mutations could be verified after a passage on RIF-containing medium, IS6110 DNA fingerprinting of 76 strains revealed eight clusters comprising 27 strains with identical restriction fragment length polymorphism patterns that mainly also show identical rpoB mutations and identical or similar drug resistance patterns. In conclusion, our results indicate that the V176F mutation should be included in molecular tests for prediction of RIF resistance in M. tuberculosis. We further demonstrated that heteroresistance caused by a mixture of mycobacterial subpopulations with different susceptibilities to RIF may influence the sensitivity of molecular tests for detection of resistance.