Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis
Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis
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DOI：
10.1128/aac.42.7.1853
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发表时间：
1998-07-01
影响因子：
4.9
通讯作者：
Gillis, TP
中科院分区：
文献类型：
--
作者：
Williams, DL;Spring, L;Gillis, TP
在29株利福平耐药临床分离株中，rpoB（编码结核分枝杆菌DNA依赖性RNA聚合酶β亚基的基因）81 bp片段内的23个插入、缺失或错义突变对利福平（利福平、利福替尼、利福喷丁和KRM-1648）耐药的贡献被确定。特异性突变rpoB等位基因导致对所有测试的利福霉素的交叉抗性的发展，而突变的子集与对利福平和利福喷丁的抗性相关，但与对KRM-1648或利福昔单抗的抗性无关。为了进一步研究特异性rpoB突变等位基因对利福霉素抗性发展的影响，将突变并入M的rpoB基因。结核病H37 Rv，包含在分枝杆菌穿梭质粒上。重组耻垢分枝含有在rpoB的密码子531或526中具有特异性突变的质粒的结核病克隆对所有测试的利福霉素表现出高水平的抗性，而含有在密码子516中具有突变的质粒的克隆对利福平和利福喷丁表现出高水平的抗性，但对利福布雷迪和KRM-1648都敏感。这些结果进一步证明了特异性rpoB突变与利福霉素耐药的发生之间的关联，并证实了先前关于rpoB基因分型用于预测利福霉素耐药表型的有用性的报道。
The contributions of 23 insertion, deletion, or missense mutations within an 81-bp fragment of rpoB, the gene encoding the beta-subunit of the DNA-dependent RNA polymerase of Mycobacterium tuberculosis, to the development of resistance to rifamycins (rifampin, rifabutin, rifapentine, and KRM-1648) in 29 rifampin-resistant clinical isolates were defined. Specific mutant rpoB alleles led to the development of cross-resistance to all rifamycins tested, while a subset of mutations were associated with resistance to rifampin and rifapentine but not to KRM-1648 or rifabutin, To further study the impact of specific rpoB mutant alleles on the development of rifamycin resistance, mutations were incorporated into the rpoB gene of M. tuberculosis H37Rv, contained on a mycobacterial shuttle plasmid, by in vitro mutagenesis. Recombinant M. tuberculosis clones containing plasmids with specific mutations in either codon 531 or 526 of rpoB exhibited high-level resistance to all rifamycins tested, whereas clones containing a plasmid with a mutation in codon 516 exhibited high-level resistance to rifampin and rifapentine but were susceptible to both rifabutin and KRM-1648. These results provided additional proof of the association of specific rpoB mutations with the development of rifamycin resistance and corroborate previous reports of the usefulness of rpoB genotyping for predicting rifamycin-resistant phenotypes.