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

Virulence. 2018;9(1):1314-1337. doi: 10.1080/21505594.2018.1496778.

Abstract

Streptococcus suis (S. suis) causes meningitis, arthritis and endocarditis in piglets. The aim of this study was to characterize the IgM degrading enzyme of S. suis (IdeSsuis) 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 IdeSsuis abrogated IgM cleavage completely. In contrast to wt rIdeSsuis, point mutated rIdeSsuis_C195S did not reduce complement-mediated hemolysis indicating that complement inhibition by rIdeSsuis depends on the IgM proteolytic activity. A S. suis mutant expressing IdeSsuis_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 S. suis in porcine blood ex vivo and mediated complement evasion as demonstrated by blood survival and C3 deposition assays including the comparative addition of rIdeSsuis and rIdeSsuis_C195S. However, experimental infection of piglets disclosed no significant differences in virulence between S. suis wt and isogenic mutants without IgM cleavage activity. This work revealed for the first time in vivo labeling of S. suis with IgM in the cerebrospinal fluid of piglets with meningitis. In conclusion, this study classifies IdeSsuis 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.

Keywords: IdeS-family protease; IdeSsuis; IgM; Streptococcus suis; cysteine protease; opsonization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Binding Sites, Antibody
  • Complement System Proteins / immunology*
  • Cysteine Proteases / genetics
  • Cysteine Proteases / immunology*
  • Host-Pathogen Interactions / immunology
  • Immune Evasion*
  • Immunoglobulin M / immunology
  • Immunoglobulin M / metabolism*
  • Meningitis / cerebrospinal fluid
  • Meningitis / microbiology
  • Mutagenesis
  • Proteolysis
  • Serogroup
  • Streptococcal Infections / blood
  • Streptococcal Infections / immunology
  • Streptococcus suis / enzymology*
  • Streptococcus suis / immunology*
  • Swine
  • Swine Diseases / microbiology

Substances

  • Bacterial Proteins
  • Immunoglobulin M
  • Complement System Proteins
  • Cysteine Proteases

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft [DFG BA 4730/3-1].