sarZ, a sarA Family Gene, Is Transcriptionally Activated by MgrA and Is Involved in the Regulation of Genes Encoding Exoproteins in Staphylococcus aureus

sarZ, a sarA Family Gene, Is Transcriptionally Activated by MgrA and Is Involved in the Regulation of Genes Encoding Exoproteins in Staphylococcus aureus
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DOI:
10.1128/jb.01555-08
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发表时间:
2009-03-01
影响因子:
3.2
通讯作者:
Manna, Adhar C.
Manna, Adhar C.
中科院分区:
生物学3区
文献类型:
--
作者:
Ballal, Anand;Ray, Binata;Manna, Adhar C.

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参与金黄色葡萄球菌致病的基因的表达受全局调控位点控制,包括双组分调控系统和转录调控因子(例如,转录因子)。例如,在一个实施例中,SAR家族基因)。SarA家族的大多数成员已被部分表征,并显示可调节大量靶基因。在这里,我们描述了sarZ,一个sarA parasynthesis从S。金黄色葡萄球菌及其家族其他成员之间的调节关系。sarZ的表达具有生长阶段依赖性,在指数生长早期表达最高。在mgrA突变体中sarZ的转录减少,并在补充的mgrA突变体菌株中恢复到正常水平,这表明mgrA作为sarZ转录的激活剂。纯化的MgrA蛋白结合到sarZ启动子区域,如通过凝胶位移测定所确定的。在分析的sarA家族基因中,sarZ的失活增加了sarS的转录,而它降低了agr的转录。在sarZ与mgrA、sarX和agr的单突变体和双突变体中评估了参与毒力的潜在靶基因的表达。北方和酶谱分析表明,sarZ基因产物在调节几个毒力基因,特别是那些编码外蛋白的基因中发挥了作用。凝胶迁移实验表明,纯化的SarZ蛋白的非特异性结合的sarZ调节的靶基因的启动子区。这些结果表明SarZ在控制S.金黄色。
The expression of genes involved in the pathogenesis of Staphylococcus aureus is controlled by global regulatory loci, including two-component regulatory systems and transcriptional regulators (e. g., sar family genes). Most members of the SarA family have been partially characterized and shown to regulate a large numbers of target genes. Here, we describe the characterization of sarZ, a sarA paralog from S. aureus, and its regulatory relationship with other members of its family. Expression of sarZ was growth phase dependent with maximal expression in the early exponential phase of growth. Transcription of sarZ was reduced in an mgrA mutant and returned to a normal level in a complemented mgrA mutant strain, which suggests that mgrA acts as an activator of sarZ transcription. Purified MgrA protein bound to the sarZ promoter region, as determined by gel shift assays. Among the sarA family of genes analyzed, inactivation of sarZ increased sarS transcription, while it decreased agr transcription. The expression of potential target genes involved in virulence was evaluated in single and double mutants of sarZ with mgrA, sarX, and agr. Northern and zymogram analyses indicated that the sarZ gene product played a role in regulating several virulence genes, particularly those encoding exoproteins. Gel shift assays demonstrated nonspecific binding of purified SarZ protein to the promoter regions of the sarZ-regulated target genes. These results demonstrate the important role played by SarZ in controlling regulatory and virulence gene expression in S. aureus.