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Journal of Bacteriology, April 2009, p. 2601-2612, Vol. 191, No. 8
0021-9193/09/$08.00+0 doi:10.1128/JB.01309-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
The Orphan Response Regulator CovR: a Globally Negative Modulator of Virulence in Streptococcus suis Serotype 2
,
Xiuzhen Pan,1,2,
Junchao Ge,1,2,
Ming Li,3,5,
Bo Wu,4,
Changjun Wang,1,
Jing Wang,1
Youjun Feng,5
Zhimin Yin,2
Feng Zheng,1
Gong Cheng,1
Wen Sun,1,2
Hongfeng Ji,1,2
Dan Hu,1,3
Peiju Shi,1,2
Xiaodan Feng,1
Xina Hao,1,2
Ruiping Dong,1
Fuquan Hu,3* and
Jiaqi Tang1*
Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing 210002, China,1 College of Life Science, Nanjing Normal University, Nanjing 210046, China,2 Department of Microbiology, Third Military Medical University, Chongqing 400038, China,3 Department of Pathology, Jinling Hospital of Nanjing, Nanjing 210002, China,4 Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China5
Received 16 September 2008/ Accepted 20 January 2009
Streptococcus suis serotype 2 is an emerging zoonotic pathogen responsible for a wide range of life-threatening diseases in pigs and humans. However, the pathogenesis of S. suis serotype 2 infection is not well understood. In this study, we report that an orphan response regulator, CovR, globally regulates gene expression and negatively controls the virulence of S. suis 05ZYH33, a streptococcal toxic shock syndrome (STSS)-causing strain. A covR-defective (
covR) mutant of 05ZYH33 displayed dramatic phenotypic changes, such as formation of longer chains, production of thicker capsules, and increased hemolytic activity. Adherence of the covR mutant to epithelial cells was greatly increased, and its resistance to phagocytosis and killing by neutrophils and monocytes was also significantly enhanced. More importantly, inactivation of covR increased the lethality of S. suis serotype 2 in experimental infection of piglets, and this phenotype was restored by covR complementation. Colonization experiments also showed that the covR mutant exhibited an increased ability to colonize susceptible tissues of piglets. The pleiotropic phenotype of the covR mutant is in full agreement with the large number of genes controlled by CovR as revealed by transcription profile analysis: 2 genes are positively regulated, and 193 are repressed, including many that encode known or putative virulence factors. These findings suggested that CovR is a global repressor in virulence regulation of STSS-causing S. suis serotype 2.
* Corresponding author. Mailing address for Jiaqi Tang: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China. Phone: 86-25-84506002. Fax: 86-25-84507094. E-mail: tjq85{at}hotmail.com. Mailing address for Fuquan Hu: Department of Microbiology, Third Military Medical University, Chongqing, 400038, China. Phone and fax: 86-23-68752240. E-mail: hufuquan{at}yahoo.com
Published ahead of print on 30 January 2009.
Supplemental material for this article may be found at http://jb.asm.org/.
X.P, J.G., M.L., B.W., and C.W. contributed equally to this work.
Journal of Bacteriology, April 2009, p. 2601-2612, Vol. 191, No. 8
0021-9193/09/$08.00+0 doi:10.1128/JB.01309-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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