Adaptation of metabolism and virulence of Streptococcus suis to host environments

猪链球菌是一种主要的猪和人畜共患病病原体，可引起败血症、脑膜炎、关节炎、心内膜炎和中毒性休克综合征。目前对猪链球菌寄主适应机制知之甚少，对其代谢和毒力调控的研究也很少。在我们的项目中，我们将分析一种高毒力的猪链球菌菌株对寄主在殖民和入侵期间可能遇到的条件的适应性。我们在以前的工作中发现的两种代谢调节剂CCPA和FlpS将特别引起人们的兴趣，因为它们似乎分别对猪链球菌适应葡萄糖和氧气供应的变化至关重要。重点将放在可能的情景上，反映在粘膜表面生长过程中代谢和毒力的变化，以及对血液循环系统和脑脊液(CSF)的入侵。这些环境将在体外模拟猪链球菌在特定条件下的生长，在恒化器中具有不同的葡萄糖和氧气利用率，并通过在猪唾液、血液和脑脊液中培养细菌。将通过分析毒力和全基因表达、蛋白质谱，以及通过比较代谢调节因子CCPA和FlpS存在缺陷的野生型和突变株来监测变化。CCPA和FlpS与体内定植和侵袭的相关性将通过这些菌株对小鼠的实验感染来评估。

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.