Involvement of the pleiotropic regulator CcpA in the physiology and stress response of the pathogen Streptococcus agalactiae

Session : BactériologieInternational audienceStreptococcus agalactiae is a leading cause of infections in neonates. This opportunistic pathogen colonizes the vagina where it has to cope with acid pH and hydrogen peroxide produced by lactobacilli. Thus, in the host, this bacterium has the necessity to set up numerous adaptation mechanisms of which the pleiotropic regulators are part. Notably, several studies have shown links between regulation of carbon metabolism and mechanisms of adaptation and virulence. This is the case of the transcriptional regulator CcpA (catabolite control protein A) that has previously been demonstrated as a major regulator involved in carbon catabolite repression in Gram-positive bacteria. This pleiotropic regulator regulates genes involved in carbon metabolism but also in other numerous mechanisms. By a transcriptomic analysis, we highlighted here that CcpA regulates 13.5% of the genome. We confirmed by electrophoretic mobility shift assays (EMSAs) that the DNA binding sites called cis-acting catabolite responsive element (cre) determined for other streptococci was effective in S. agalactiae. We reported here that CcpA is of capital importance for survival in acid and oxidative stresses, and is implicated in macrophages survival by regulating several genes putatively or already described as involved in stress response. Among them, we focused our study on SAK_1689 that codes for a putative UspA protein. We first demonstrated that SAK_1689, highly repressed by CcpA, is overexpressed in oxidative stress. We showed that the overexpression in the ∆ccpAmutant under oxidative stress was harmful for the bacterium