The Orphan Response Regulator CovR: a Globally Negative Modulator of Virulence in Streptococcus suis Serotype 2
The Orphan Response Regulator CovR: a Globally Negative Modulator of Virulence in Streptococcus suis Serotype 2
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孤儿反应调节因子 CovR：猪链球菌血清型 2 毒力的全局负调节因子
DOI：
10.1128/jb.01309-08
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发表时间：
2009-04-15
影响因子：
3.2
通讯作者：
Tang, Jiaqi
中科院分区：
文献类型：
--
作者：
Pan, Xiuzhen;Ge, Junchao;Tang, Jiaqi
猪链球菌血清型 2 是一种新兴的人畜共患病原体，可导致猪和人类出现多种危及生命的疾病。然而，猪链球菌血清型2感染的发病机制尚不清楚。在这项研究中，我们报道了一种孤儿反应调节因子 CovR，它可以全局调节基因表达并负向控制猪链球菌 05ZYH33（一种链球菌中毒性休克综合征 (STSS) 致病菌株）的毒力。 05ZYH33 的 covR 缺陷型 (Delta covR) 突变体表现出显着的表型变化，例如形成更长的链、产生更厚的胶囊和增加的溶血活性。 Delta covR突变体对上皮细胞的粘附大大增加，其对中性粒细胞和单核细胞吞噬和杀伤的抵抗力也显着增强。更重要的是，covR的失活增加了猪链球菌血清型2在实验性感染仔猪中的致死率，并且这种表型通过covR的互补得以恢复。定植实验还表明，Delta covR 突变体表现出在仔猪易感组织中定植的能力增强。转录谱分析显示，Delta covR 突变体的多效性表型与 CovR 控制的大量基因完全一致：2 个基因受到正向调节，193 个基因受到抑制，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 的猪链球菌血清型 2 毒力调节的全局抑制因子。
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 (Delta 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 Delta 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 Delta covR mutant exhibited an increased ability to colonize susceptible tissues of piglets. The pleiotropic phenotype of the Delta 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.