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IdeS, a secreted proteinase of Streptococcus pyogenes, is bound to a nuclease at the bacterial surface where it inactivates opsonizing IgG antibodies

Frick, Inga Maria LU ; Happonen, Lotta LU ; Wrighton, Sebastian LU orcid ; Nordenfelt, Pontus LU orcid and Björck, Lars LU (2023) In Journal of Biological Chemistry 299(11). p.1-16
Abstract

The important bacterial pathogen Streptococcus pyogenes secretes IdeS (immunoglobulin G-degrading enzyme of S. pyogenes), a proteinase that cleaves human immunoglobulin G (IgG) antibodies in the hinge region resulting in Fc (fragment crystallizable) and F(ab')2 (fragment antigen-binding) fragments and protects the bacteria against phagocytic killing. Experiments with radiolabeled IdeS and flow cytometry demonstrated that IdeS binds to the surface of S. pyogenes, and the interaction was most prominent in conditions resembling those in the pharynx (acidic pH and low salt), the habitat for S. pyogenes. SpnA (S. pyogenes nuclease A) is a cell wall–anchored DNase. A dose-dependent interaction between purified SpnA and IdeS was... (More)

The important bacterial pathogen Streptococcus pyogenes secretes IdeS (immunoglobulin G-degrading enzyme of S. pyogenes), a proteinase that cleaves human immunoglobulin G (IgG) antibodies in the hinge region resulting in Fc (fragment crystallizable) and F(ab')2 (fragment antigen-binding) fragments and protects the bacteria against phagocytic killing. Experiments with radiolabeled IdeS and flow cytometry demonstrated that IdeS binds to the surface of S. pyogenes, and the interaction was most prominent in conditions resembling those in the pharynx (acidic pH and low salt), the habitat for S. pyogenes. SpnA (S. pyogenes nuclease A) is a cell wall–anchored DNase. A dose-dependent interaction between purified SpnA and IdeS was demonstrated in slot binding and surface plasmon resonance spectroscopy experiments. Gel filtration showed that IdeS forms proteolytically active complexes with SpnA in solution, and super-resolution fluorescence microscopy revealed the presence of SpnA–IdeS complexes at the surface of S. pyogenes. Finally, specific IgG antibodies binding to S. pyogenes surface antigens were efficiently cleaved by surface-associated IdeS. IdeS is secreted by all S. pyogenes isolates and cleaves IgG antibodies with a unique degree of specificity and efficiency. These properties and the finding here that the proteinase is present and fully active at the bacterial surface in complex with SpnA implicate an important role for IdeS in S. pyogenes biology and pathogenesis.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bacteria, DNase, IdeS, IgG, immunity, proteinase, proteolysis, Streptococcus, virulence
in
Journal of Biological Chemistry
volume
299
issue
11
article number
105345
pages
1 - 16
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:37838172
  • scopus:85175611861
ISSN
0021-9258
DOI
10.1016/j.jbc.2023.105345
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Authors
id
6401930e-02cd-42a0-8039-8662ea45d9f1
date added to LUP
2023-11-19 08:28:26
date last changed
2024-04-16 15:08:28
@article{6401930e-02cd-42a0-8039-8662ea45d9f1,
  abstract     = {{<p>The important bacterial pathogen Streptococcus pyogenes secretes IdeS (immunoglobulin G-degrading enzyme of S. pyogenes), a proteinase that cleaves human immunoglobulin G (IgG) antibodies in the hinge region resulting in Fc (fragment crystallizable) and F(ab')<sub>2</sub> (fragment antigen-binding) fragments and protects the bacteria against phagocytic killing. Experiments with radiolabeled IdeS and flow cytometry demonstrated that IdeS binds to the surface of S. pyogenes, and the interaction was most prominent in conditions resembling those in the pharynx (acidic pH and low salt), the habitat for S. pyogenes. SpnA (S. pyogenes nuclease A) is a cell wall–anchored DNase. A dose-dependent interaction between purified SpnA and IdeS was demonstrated in slot binding and surface plasmon resonance spectroscopy experiments. Gel filtration showed that IdeS forms proteolytically active complexes with SpnA in solution, and super-resolution fluorescence microscopy revealed the presence of SpnA–IdeS complexes at the surface of S. pyogenes. Finally, specific IgG antibodies binding to S. pyogenes surface antigens were efficiently cleaved by surface-associated IdeS. IdeS is secreted by all S. pyogenes isolates and cleaves IgG antibodies with a unique degree of specificity and efficiency. These properties and the finding here that the proteinase is present and fully active at the bacterial surface in complex with SpnA implicate an important role for IdeS in S. pyogenes biology and pathogenesis.</p>}},
  author       = {{Frick, Inga Maria and Happonen, Lotta and Wrighton, Sebastian and Nordenfelt, Pontus and Björck, Lars}},
  issn         = {{0021-9258}},
  keywords     = {{bacteria; DNase; IdeS; IgG; immunity; proteinase; proteolysis; Streptococcus; virulence}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1--16}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{IdeS, a secreted proteinase of Streptococcus pyogenes, is bound to a nuclease at the bacterial surface where it inactivates opsonizing IgG antibodies}},
  url          = {{http://dx.doi.org/10.1016/j.jbc.2023.105345}},
  doi          = {{10.1016/j.jbc.2023.105345}},
  volume       = {{299}},
  year         = {{2023}},
}