IgM cleavage by <i>Streptococcus suis</i> reduces IgM bound to the bacterial surface and is a novel complement evasion mechanism

<i>Streptococcus suis</i> (<i>S. suis</i>) causes meningitis, arthritis and endocarditis in piglets. The aim of this study was to characterize the IgM degrading enzyme of <i>S. suis</i> (Ide<i>_Ssuis</i>) and to investigate the role of IgM cleavage in evasion of the classical complement pathway and pathogenesis. Targeted mutagenesis of a cysteine in the putative active center of Ide<i>_Ssuis</i> abrogated IgM cleavage completely. In contrast to wt rIde<i>_Ssuis</i>, point mutated rIde<i>_Ssuis</i>_C195S did not reduce complement-mediated hemolysis indicating that complement inhibition by rIde<i>_Ssuis</i> depends on the IgM proteolytic activity. A <i>S. suis</i> mutant expressing Ide<i>_Ssuis</i>_C195S did not reduce IgM labeling, whereas the wt and complemented mutant showed less IgM F(ab’)2 and IgM Fc antigen on the surface. IgM cleavage increased survival of <i>S. suis</i> in porcine blood <i>ex vivo</i> and mediated complement evasion as demonstrated by blood survival and C3 deposition assays including the comparative addition of rIde<i>_Ssuis</i> and rIde<i>_Ssuis</i>_C195S. However, experimental infection of piglets disclosed no significant differences in virulence between <i>S. suis</i> wt and isogenic mutants without IgM cleavage activity. This work revealed for the first time <i>in vivo</i> labeling of <i>S. suis</i> with IgM in the cerebrospinal fluid of piglets with meningitis. In conclusion, this study classifies Ide<i>_Ssuis</i> as a cysteine protease and emphasizes the role of IgM cleavage for bacterial survival in porcine blood and complement evasion though IgM cleavage is not crucial for the pathogenesis of serotype 2 meningitis.