Adaptation of metabolism and virulence of Streptococcus suis to host environments

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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.