Pan Xiuzhen, Ge Junchao, Li Ming, Wu Bo, Wang Changjun, Wang Jing, Feng Youjun, Yin Zhimin, Zheng Feng, Cheng Gong, Sun Wen, Ji Hongfeng, Hu Dan, Shi Peiju, Feng Xiaodan, Hao Xina, Dong Ruiping, Hu Fuquan, Tang Jiaqi
Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 210002, China.
J Bacteriol. 2009 Apr;191(8):2601-12. doi: 10.1128/JB.01309-08. Epub 2009 Jan 30.
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 (DeltacovR) mutant of 05ZYH33 displayed dramatic phenotypic changes, such as formation of longer chains, production of thicker capsules, and increased hemolytic activity. Adherence of the DeltacovR 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 DeltacovR mutant exhibited an increased ability to colonize susceptible tissues of piglets. The pleiotropic phenotype of the DeltacovR 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.
猪链球菌2型是一种新出现的人畜共患病原体，可导致猪和人类出现多种危及生命的疾病。然而，猪链球菌2型感染的发病机制尚不清楚。在本研究中，我们报告了一个孤儿应答调节因子CovR，它可全局调控基因表达，并对引起链球菌中毒性休克综合征（STSS）的菌株猪链球菌05ZYH33的毒力起负调控作用。05ZYH33的CovR缺陷型（DeltacovR）突变体表现出显著的表型变化，如形成更长的链、产生更厚的荚膜以及溶血活性增加。DeltacovR突变体对上皮细胞的黏附力大大增加，其对中性粒细胞和单核细胞吞噬及杀伤的抗性也显著增强。更重要的是，CovR失活增加了猪链球菌2型在仔猪实验性感染中的致死率，而这种表型可通过CovR互补得以恢复。定殖实验还表明，DeltacovR突变体在仔猪易感组织中的定殖能力增强。转录谱分析显示，DeltacovR突变体的多效性表型与CovR控制的大量基因完全一致：2个基因被正向调控，193个基因被抑制，其中包括许多编码已知或推定毒力因子的基因。这些发现表明，CovR是引起STSS的猪链球菌2型毒力调控中的全局抑制因子。
