PrsA contributes to Streptococcus suis serotype 2 pathogenicity by modulating secretion of selected virulence factors

Abstract

Streptococcus suis serotype 2 (S. suis 2) is a major zoonotic pathogen. Parvulin-type peptidyl-prolyl isomerase (PrsA) in S. suis 2 is found surface-associated, pro-inflammatory and cytotoxic. To further explore the roles of PrsA in S. suis 2 infection, we constructed a prsA deletion mutant (ΔprsA) and a complemented strain (CΔprsA). The ΔprsA mutant showed increased length of bacterial chains and decreased growth. Deletion of prsA increased bacterial adhesion to host epithelial cells but with weakened invasion. The ΔprsA mutant had reduced survival in RAW264.7 macrophages and pig whole blood, and significantly attenuated in virulence to mice. All these phenotypes of the mutant could be reversed largely to the levels of its parental strain by gene complementation. Western blotting revealed that suilysin was markedly reduced both in surface-associated (SAP) and secreted fractions (SecP) of ΔprsA, which might be responsible for reduced hemolytic activity. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and enolase were significantly increased in both SAP and SecP fractions as a result of prsA deletion. Increased adhesion of the ΔprsA mutant to bEND.3 cells was prevented using polyclonal antibodies against GAPDH and enolase. Overall, we propose that S. suis 2 deploys PrsA to control translocation of important virulence factors, thereby favoring its survival in the host with enhanced pathogenicity by compromising its interactions with the host cells. Further investigation is required to find out how PrsA modulates protein translocation to benefit S. suis infection and if there are other S. suis 2 substrates of potential virulence regulated by PrsA.