Regulation of VanB-type vancomycin resistance gene expression by the VanS(B)-VanR(B) two-component regulatory system in Enterococcus faecalis V583
Regulation of VanB-type vancomycin resistance gene expression by the VanS(B)-VanR(B) two-component regulatory system in Enterococcus faecalis V583
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DOI：
10.1128/jb.178.5.1302-1309.1996
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发表时间：
1996-03-01
影响因子：
3.2
通讯作者：
Courvalin, P
中科院分区：
文献类型：
--
作者：
Evers, S;Courvalin, P
肠球菌中获得性VanA和VanB型糖肽耐药是由于终止于D-乳酸的修饰的肽聚糖前体的合成，与对万古霉素和替考拉宁均耐药的VanA型菌株相反，VanB型菌株仍然对替考拉宁敏感。我们已经确定了7，粪肠球菌V583中与VanB型耐药相关的160 bp DNA片段，包含7个开放阅读框，远端编码VanH（B），VanB，和VanX（B）蛋白，它们与推测的负责VanA型抗性的VanH、VanA和VanX蛋白高度相似，这些蛋白的结构基因的上游是编码D，D-羧肽酶和具有未知功能的开放阅读框vanW的vanY（B）基因，基因簇的近端部分编码表观的VanS（B）-VanR（B）双组分调控系统。VanR（B）与OmpR亚类的反应调节因子相关，VanS（B）与膜相关组氨酸蛋白激酶相关。用报告基因和启动子作图分析转录融合物表明VanR（B）-VanS（B）双组分调控系统激活位于vanS（B）基因下游的启动子。万古霉素而非替考拉宁是诱导剂，这解释了VanB型肠球菌对替考拉宁的敏感性。
Acquired VanA- and VanB-type glycopeptide resistance in enterococci is due to synthesis of modified peptidoglycan precursors terminating in D-lactate, As opposed to VanA-type strains which are resistant to both vancomycin and teicoplanin, VanB-type strains remain teicoplanin susceptible, We have determined the sequence of a 7,160-bp DNA fragment associated with VanB-type resistance in Enterococcus faecalis V583 that contains seven open reading frames, The distal part encoded the VanH(B), VanB, and VanX(B) proteins that are highly similar to the putative VanH, VanA, and VanX proteins responsible for VanA-type resistance, Upstream from the structural genes for these proteins were the vanY(B) gene encoding a D,D-carboxypeptidase and an open reading frame vanW with an unknown function, The proximal part of the gene cluster coded for the apparent VanS(B)-VanR(B) two-component regulatory system. VanR(B) was related to response regulators of the OmpR subclass, and VanS(B) was related to membrane-associated histidine protein kinases. Analysis of transcriptional fusions with a reporter gene and promoter mapping indicated that the VanR(B)-VanS(B) two-component regulatory system activates a promoter located immediately downstream from the vanS(B) gene. Vancomycin, but not teicoplanin, was an inducer, which explains teicoplanin susceptibility of VanB-type enterococci.