THE VANS-VANR 2-COMPONENT REGULATORY SYSTEM CONTROLS SYNTHESIS OF DEPSIPEPTIDE PEPTIDOGLYCAN PRECURSORS IN ENTEROCOCCUS-FAECIUM BM4147
THE VANS-VANR 2-COMPONENT REGULATORY SYSTEM CONTROLS SYNTHESIS OF DEPSIPEPTIDE PEPTIDOGLYCAN PRECURSORS IN ENTEROCOCCUS-FAECIUM BM4147
复制标题
DOI：
10.1128/jb.174.8.2582-2591.1992
复制
发表时间：
1992-04-01
影响因子：
3.2
通讯作者：
COURVALIN, P
中科院分区：
文献类型：
--
作者：
ARTHUR, M;MOLINAS, C;COURVALIN, P
屎肠球菌BM 4147的质粒pIP 816赋予对万古霉素的可诱导抗性，并编码用于合成含缩肽的肽聚糖前体的VanH脱氢酶和VanA连接酶，所述肽聚糖前体以降低的亲和力结合抗生素。 我们已经表征了pIP 816的五个基因的簇，其足以在万古霉素存在下进行肽聚糖合成。 货车簇的远端部分编码VanH、VanA和第三种酶VanX，所有这些都是抗性所必需的。 这些酶的合成调控在转录水平上的VanS-VanR双组分调控系统编码的近端部分的集群。 VanR是一种与OmpR亚类的反应调节因子相关的转录激活因子。 VanS刺激VanR依赖性转录，并与控制反应调节剂磷酸化水平的膜相关组氨酸蛋白激酶有关。 与报告基因和RNA图谱的转录融合分析表明，VanR-VanS双组分调控系统激活用于vanH，vanA和vanX抗性基因共转录的启动子。
Plasmid pIP816 of Enterococcus faecium BM4147 confers inducible resistance to vancomycin and encodes the VanH dehydrogenase and the VanA ligase for synthesis of depsipeptide-containing peptidoglycan precursors which bind the antibiotic with reduced affinity. We have characterized a cluster of five genes of pIP816 sufficient for peptidoglycan synthesis in the presence of vancomycin. The distal part of the van cluster encodes VanH, VanA, and a third enzyme, VanX, all of which are necessary for resistance. Synthesis of these enzymes was regulated at the transcriptional level by the VanS-VanR two-component regulatory system encoded by the proximal part of the cluster. VanR was a transcriptional activator related to response regulators of the OmpR subclass. VanS stimulated VanR-dependent transcription and was related to membrane-associated histidine protein kinases which control the level of phosphorylation of response regulators. Analysis of transcriptional fusions with a reporter gene and RNA mapping indicated that the VanR-VanS two-component regulatory system activates a promoter used for cotranscription of the vanH, vanA, and vanX resistance genes.