title: EndoS and SpeB from Streptococcus pyogenes inhibit immunoglobulin-mediated opsonophagocytosis.
abstract: The human pathogen Streptococcus pyogenes primarily infects the upper respiratory tract and skin, but occasionally it disseminates and causes severe invasive disease with high mortality. This study revealed that the activity of extracellular EndoS, which hydrolyzes the functionally important N-linked oligosaccharides on opsonizing immunoglobulin G (IgG), contributes to increased survival of S. pyogenes in human blood ex vivo. The inability to kill the bacteria is due to reduced binding of IgG to Fc receptors and impaired classical pathway-mediated activation of complement. In addition, the activity of extracellular SpeB, which cleaves IgG into Fc and Fab fragments, also increases bacterial survival. This suggests that S. pyogenes expresses two enzymes, EndoS and SpeB, which modulate IgG by different mechanisms in order to evade the adaptive immune system.
authors.affiliation: Department of Cell and Molecular Biology, Lund University, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Collin
authors.forename: Mikael D
authors.initials: MD
authors.lastname: Svensson
authors.forename: Anders G
authors.initials: AG
authors.lastname: Sjöholm
authors.forename: Jens C
authors.initials: JC
authors.lastname: Jensenius
authors.forename: Ulf
authors.initials: U
authors.lastname: Sjöbring
authors.forename: Arne
authors.initials: A
authors.lastname: Olsén
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001769:Blood / Q000382:microbiology; D003167:Complement Activation; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D009895:Opsonin Proteins; D010587:Phagocytosis / Q000276:immunology*; D011961:Receptors, Fc / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D011961:Receptors, Fc; D006026:Glycoside Hydrolases; C431325:NDOS protein, Streptococcus pyogenes; D003546:Cysteine Endopeptidases; C042477:streptopain