Adaptation of metabolism and virulence of Streptococcus suis to host environments

猪链球菌的代谢和毒力对宿主环境的适应

• 批准号: 201699376
• 负责人: Professor Dr. Ralph Goethe
• 金额: --
• 依托单位: Institut für Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/201699376?language=en
• 关键词: Adaptation; metabolism; virulence; Streptococcus; suis

Streptococcus suis is a major porcine and zoonotic pathogen causing septicemia, meningitis, arthritis, endocarditis, and toxic-shock-like syndrome. Little is known about mechanisms of host adaptation of S. suis, and metabolic and virulence regulation have barely been studied. In our project we will analyse adaptation of a highly virulent S. suis strain to conditions putatively encountered during colonization and invasion of the host. Two metabolic regulators which we have identified in previous work, CcpA and FlpS, will be of particular interest, since they seem to be crucial for adaptation of S. suis to changing glucose and oxygen availability, respectively. Focus will be on possible scenarios reflecting changes in metabolism and virulence during growth on mucosal surfaces, and invasion in the blood circulation system and the cerebrospinal fluid (CSF). These environments will be mimicked in vitro by growth of S. suis under defined conditions with different glucose and oxygen availability in a chemostat, and by incubation of bacteria in porcine saliva, blood and CSF. Changes will be monitored by analysing virulence and whole gene expression, protein profiles and by comparing wildtype with mutant strains which are defective in the metabolic regulators CcpA and FlpS. The relevance of CcpA and FlpS for in vivo colonization and invasion will be evaluated by experimental mouse infections with these strains.

猪链球菌是引起猪败血症、脑膜炎、关节炎、心内膜炎和中毒性休克样综合征的主要病原体。目前对S.猪，代谢和毒力调节几乎没有研究。在我们的项目中，我们将分析适应一个高度致命的S。suis菌株在宿主的定殖和入侵期间遇到的条件。我们在以前的工作中发现的两个代谢调节因子，CcpA和FlpS，将特别令人感兴趣，因为它们似乎对S的适应至关重要。分别改变葡萄糖和氧气的可用性。重点将放在可能的情况下，反映在粘膜表面生长过程中的代谢和毒力的变化，并在血液循环系统和脑脊液（CSF）的入侵。这些环境将通过S.在恒化器中具有不同葡萄糖和氧气可用性的限定条件下，以及通过在猪唾液、血液和CSF中孵育细菌，将通过分析毒力和全基因表达、蛋白质谱以及通过比较野生型与代谢调节因子CcpA和FlpS缺陷的突变菌株来监测变化。CcpA和FlpS与体内定殖和侵袭的相关性将通过用这些菌株感染实验小鼠来评价。