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

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

Author information

1
a Institute for Bacteriology and Mycology, Centre for Infectious Diseases, Veterinary Faculty , University of Leipzig , Leipzig , Germany.
2
b Institute of Immunology, Centre for Infectious Diseases, Veterinary Faculty , University of Leipzig , Leipzig , Germany.
3
c Department of Physiological Chemistry and Research Center for Emerging Infections and Zoonoses (RIZ) , University of Veterinary Medicine Hannover , Hannover , Germany.
4
d Central Facility for Microscopy , Helmholtz Centre for Infection Research , Braunschweig , Germany.
5
e Department of Neuropathology , University Medical Center Göttingen, Georg-August-University Göttingen , Göttingen , Germany.
6
f Department of Geriatrics , Evangelisches Krankenhaus Göttingen-Weende , Göttingen , Germany.
7
g Institute for Microbiology, Centre for Infection Medicine , University of Veterinary Medicine Hannover , Hanover , Germany.
8
h Institute of Immunology , University of Heidelberg , Heidelberg , Germany.
9
i Department of Pathology , University of Veterinary Medicine Hannover , Hannover , Germany.

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

PMID:
30001174
PMCID:
PMC6177247
DOI:
10.1080/21505594.2018.1496778
[Indexed for MEDLINE]
Free PMC Article

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