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Journal of Bacteriology, November 2008, p. 7567-7578, Vol. 190, No. 22
0021-9193/08/$08.00+0     doi:10.1128/JB.01532-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Functional Definition and Global Regulation of Zur, a Zinc Uptake Regulator in a Streptococcus suis Serotype 2 Strain Causing Streptococcal Toxic Shock Syndrome{triangledown} ,{dagger}

Youjun Feng,1,3,{ddagger} Ming Li,2,4 Huimin Zhang,1 Beiwen Zheng,1,3 Huiming Han,1,3 Changjun Wang,2 Jinghua Yan,1 Jiaqi Tang,2 and George F. Gao1*

Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China,1 Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing 210002, China,2 Graduate University, Chinese Academy of Sciences, Beijing 100049, China,3 Department of Microbiology, Third Military Medical University, Chongqing 630030, China4

Received 22 September 2007/ Accepted 7 August 2008

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.

* Corresponding author. Mailing address: Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. Phone: 86-10-64807688. Fax: 86-10-64807882. E-mail: gaof{at}im.ac.cn

{triangledown} Published ahead of print on 22 August 2008.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

{ddagger} Present address: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.

Journal of Bacteriology, November 2008, p. 7567-7578, Vol. 190, No. 22
0021-9193/08/$08.00+0     doi:10.1128/JB.01532-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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