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DOI: 10.1055/s-2006-932717
The peptidyl-prolyl isomerase SlrA contributes to virulence and adherence of Streptococcus pneumoniae
Streptococcus pneumoniae expresses two lipoproteins, which resemble homology with distinct families of peptidyl-prolyl isomerases (PPIases). The PpmA protein is homologous with the parvulin family of PPIases, whereas the streptococcal lipoprotein rotamase A (SlrA) resembles homology with the cyclophilins. In this study, we investigated the PPIase activity of SlrA and PpmA, and in particular the contribution of SlrA to virulence.
SlrA clearly displayed PPIase activity, whereas PpmA did not show detectable PPIase activity. With respect to substrate specificity of SlrA, the largest kcat/KM was determined for the alanine substrate, which is typical for prokaryotic cyclophilins.
In a murine intranasal infection model the slrA knockout strain demonstrated a significant reduction in its capacity to colonize the nasopharynx and the airways of mice compared to the isogenic wild-type strain D39. In cell culture infections the SlrA-deficiency resulted in decreased adherence to non-professional cell lines. In addition, the absence of SlrA interfered with uptake in professional phagocytes. In conclusion, SlrA is a functional cyclophilin-type PPIase and contributes to pneumococcal virulence in vivo. Finally, SlrA is particularly in a non-tissue specific manner involved in adhesion to host cells and influences pneumococcal protection against phagocytosis.