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Evasion of phagocytosis through cooperation between two ligand-binding regions in Streptococcus pyogenes M protein.

Carlsson, Fredric LU ; Berggård, Karin LU ; Stålhammar-Carlemalm, Margaretha LU and Lindahl, Gunnar LU (2003) In Journal of Experimental Medicine 198(7). p.1057-1068
Abstract
The M protein of Streptococcus pyogenes is a major bacterial virulence factor that confers resistance to phagocytosis. To analyze how M protein allows evasion of phagocytosis, we used the M22 protein, which has features typical of many M proteins and has two well-characterized regions binding human plasma proteins: the hypervariable NH2-terminal region binds C4b-binding protein (C4BP), which inhibits the classical pathway of complement activation; and an adjacent semivariable region binds IgA-Fc. Characterization of chromosomal S. pyogenes mutants demonstrated that each of the ligand-binding regions contributed to phagocytosis resistance, which could be fully explained as cooperation between the two regions. Deposition of complement on S.... (More)
The M protein of Streptococcus pyogenes is a major bacterial virulence factor that confers resistance to phagocytosis. To analyze how M protein allows evasion of phagocytosis, we used the M22 protein, which has features typical of many M proteins and has two well-characterized regions binding human plasma proteins: the hypervariable NH2-terminal region binds C4b-binding protein (C4BP), which inhibits the classical pathway of complement activation; and an adjacent semivariable region binds IgA-Fc. Characterization of chromosomal S. pyogenes mutants demonstrated that each of the ligand-binding regions contributed to phagocytosis resistance, which could be fully explained as cooperation between the two regions. Deposition of complement on S. pyogenes occurred almost exclusively via the classical pathway, even under nonimmune conditions, but was down-regulated by bacteria-bound C4BP, providing an explanation for the ability of bound C4BP to inhibit phagocytosis. Different opsonizing antisera shared the ability to block binding of both C4BP and IgA, suggesting that the two regions in M22 play important roles also under immune conditions, as targets for protective antibodies. These data indicate that M22 and similar M proteins confer resistance to phagocytosis through ability to bind two components of the human immune system. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
198
issue
7
pages
1057 - 1068
publisher
Rockefeller University Press
external identifiers
  • wos:000185860400008
  • pmid:14517274
  • scopus:0141890189
ISSN
1540-9538
DOI
language
English
LU publication?
yes
id
f9a4e43c-7a80-4d03-814a-b7d91fad7133 (old id 118384)
date added to LUP
2007-07-09 15:41:10
date last changed
2018-06-17 04:45:18
@article{f9a4e43c-7a80-4d03-814a-b7d91fad7133,
  abstract     = {The M protein of Streptococcus pyogenes is a major bacterial virulence factor that confers resistance to phagocytosis. To analyze how M protein allows evasion of phagocytosis, we used the M22 protein, which has features typical of many M proteins and has two well-characterized regions binding human plasma proteins: the hypervariable NH2-terminal region binds C4b-binding protein (C4BP), which inhibits the classical pathway of complement activation; and an adjacent semivariable region binds IgA-Fc. Characterization of chromosomal S. pyogenes mutants demonstrated that each of the ligand-binding regions contributed to phagocytosis resistance, which could be fully explained as cooperation between the two regions. Deposition of complement on S. pyogenes occurred almost exclusively via the classical pathway, even under nonimmune conditions, but was down-regulated by bacteria-bound C4BP, providing an explanation for the ability of bound C4BP to inhibit phagocytosis. Different opsonizing antisera shared the ability to block binding of both C4BP and IgA, suggesting that the two regions in M22 play important roles also under immune conditions, as targets for protective antibodies. These data indicate that M22 and similar M proteins confer resistance to phagocytosis through ability to bind two components of the human immune system.},
  author       = {Carlsson, Fredric and Berggård, Karin and Stålhammar-Carlemalm, Margaretha and Lindahl, Gunnar},
  issn         = {1540-9538},
  language     = {eng},
  number       = {7},
  pages        = {1057--1068},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Evasion of phagocytosis through cooperation between two ligand-binding regions in Streptococcus pyogenes M protein.},
  url          = {http://dx.doi.org/},
  volume       = {198},
  year         = {2003},
}