Functional Definition and Global Regulation of Zur, a Zinc Uptake Regulator in a Streptococcus suis Serotype 2 Strain Causing Streptococcal Toxic Shock Syndrome
Functional Definition and Global Regulation of Zur, a Zinc Uptake Regulator in a Streptococcus suis Serotype 2 Strain Causing Streptococcal Toxic Shock Syndrome
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DOI：
10.1128/jb.01532-07
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发表时间：
2008-11-01
影响因子：
3.2
通讯作者：
Gao, George F.
中科院分区：
文献类型：
--
作者：
Feng, Youjun;Li, Ming;Gao, George F.
锌是所有生物体必需的微量元素，在各种细胞过程中起着关键作用。然而，过量的锌对细胞极其有害。细菌已经进化出复杂的机制（如流出/流入系统），以将浓度控制在适合于维持细胞中锌稳态和适应环境的水平。Zur（锌摄取调节剂）蛋白是参与锌稳态的精确控制的这些功能成员之一。在这里，我们确定了一个zur同源物指定310从猪链球菌血清型2，菌株05 ZYH 33，一个高度侵入性的分离株引起链球菌中毒性休克综合征。生化分析表明，基因310的蛋白产物以二聚体形式存在，并携带锌离子。通过同源重组获得了310基因的一个同基因置换突变体--Delta 310突变体。生理测试表明，Delta 310突变体对Zn 2+特异性敏感，而Delta 310突变体的功能互补可以恢复其持续能力，表明310是Zur家族的功能成员。双向电泳表明，在三角洲310突变体中的9个蛋白质过表达与野生型相比。DNA微阵列分析表明，Delta 310突变体中有121个基因受到影响，其中72个基因上调，49个基因下调。对S.在高锌浓度下，猪血清2型也显示出117个差异表达基因，其中71个上调，46个下调。令人惊讶的是，超过70%的差异表达基因在Delta 310突变体中与S.猪血清型2，在响应高Zn 2+浓度时差异表达，这与310参与锌稳态的观点一致。因此，我们首次报告了一种新的锌反应调节剂，Zur，从猪链球菌血清型2。
Zinc is an essential trace element for all living organisms and plays pivotal roles in various cellular processes. However, an excess of zinc is extremely deleterious to cells. Bacteria have evolved complex machineries (such as efflux/influx systems) to control the concentration at levels appropriate for the maintenance of zinc homeostasis in cells and adaptation to the environment. The Zur (zinc uptake regulator) protein is one of these functional members involved in the precise control of zinc homeostasis. Here we identified a zur homologue designated 310 from Streptococcus suis serotype 2, strain 05ZYH33, a highly invasive isolate causing streptococcal toxic shock syndrome. Biochemical analysis revealed that the protein product of gene 310 exists as a dimer form and carries zinc ions. An isogenic gene replacement mutant of gene 310, the Delta 310 mutant, was obtained by homologous recombination. Physiological tests demonstrated that the Delta 310 mutant is specifically sensitive to Zn2+, while functional complementation of the Delta 310 mutant can restore its duration capability, suggesting that 310 is a functional member of the Zur family. Two-dimensional electrophoresis indicated that nine proteins in the Delta 310 mutant are overexpressed in comparison with those in the wild type. DNA microarray analyses suggested that 121 genes in the Delta 310 mutant are affected, of which 72 genes are upregulated and 49 are downregulated. The transcriptome of S. suis serotype 2 with high Zn2+ concentrations also showed 117 differentially expressed genes, with 71 upregulated and 46 downregulated. Surprisingly, more than 70% of the genes differentially expressed in the Delta 310 mutant were the same as those in S. suis serotype 2 that were differentially expressed in response to high Zn2+ concentration, consistent with the notion that 310 is involved in zinc homeostasis. We thus report for the first time a novel zinc-responsive regulator, Zur, from Streptococcus suis serotype 2.