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Yersinia enterocolitica serum resistance proteins YadA and Ail bind the complement regulator C4b-binding protein

Kirjavainen, Vesa; Jarva, Hanna; Biedzka-Sarek, Marta; Blom, Anna LU ; Skurnik, Mikael and Meri, Seppo (2008) In PLoS Pathogens 4(8).
Abstract
Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS) O-antigen (O-ag) and outer core (OC) do not contribute directly to complement resistance. The aim of this study was to analyze a possible mechanism whereby Y. enterocolitica could inhibit the antibody-mediated classical pathway of complement activation. We show that Y. enterocolitica serotypes O:3, O:8, and O:9 bind C4b-binding protein (C4bp), an inhibitor of... (More)
Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS) O-antigen (O-ag) and outer core (OC) do not contribute directly to complement resistance. The aim of this study was to analyze a possible mechanism whereby Y. enterocolitica could inhibit the antibody-mediated classical pathway of complement activation. We show that Y. enterocolitica serotypes O:3, O:8, and O:9 bind C4b-binding protein (C4bp), an inhibitor of both the classical and lectin pathways of complement. To identify the C4bp receptors on Y. enterocolitica serotype O:3 surface, a set of mutants expressing YadA, Ail, O-ag, and OC in different combinations was tested for the ability to bind C4bp. The studies showed that both YadA and Ail acted as C4bp receptors. Ail-mediated C4bp binding, however, was blocked by the O-ag and OC, and could be observed only with mutants lacking these LPS structures. C4bp bound to Y. enterocolitica was functionally active and participated in the factor I-mediated degradation of C4b. These findings show that Y. enterocolitica uses two proteins, YadA and Ail, to bind C4bp. Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
PLoS Pathogens
volume
4
issue
8
publisher
Public Library of Science
external identifiers
  • wos:000259783100028
  • scopus:50849105103
ISSN
1553-7366
DOI
10.1371/journal.ppat.1000140
language
English
LU publication?
yes
id
e5922cf6-489d-42a5-997c-4fc9a5a21798 (old id 1285114)
date added to LUP
2009-02-06 10:48:18
date last changed
2017-04-09 03:42:08
@article{e5922cf6-489d-42a5-997c-4fc9a5a21798,
  abstract     = {Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS) O-antigen (O-ag) and outer core (OC) do not contribute directly to complement resistance. The aim of this study was to analyze a possible mechanism whereby Y. enterocolitica could inhibit the antibody-mediated classical pathway of complement activation. We show that Y. enterocolitica serotypes O:3, O:8, and O:9 bind C4b-binding protein (C4bp), an inhibitor of both the classical and lectin pathways of complement. To identify the C4bp receptors on Y. enterocolitica serotype O:3 surface, a set of mutants expressing YadA, Ail, O-ag, and OC in different combinations was tested for the ability to bind C4bp. The studies showed that both YadA and Ail acted as C4bp receptors. Ail-mediated C4bp binding, however, was blocked by the O-ag and OC, and could be observed only with mutants lacking these LPS structures. C4bp bound to Y. enterocolitica was functionally active and participated in the factor I-mediated degradation of C4b. These findings show that Y. enterocolitica uses two proteins, YadA and Ail, to bind C4bp. Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host.},
  author       = {Kirjavainen, Vesa and Jarva, Hanna and Biedzka-Sarek, Marta and Blom, Anna and Skurnik, Mikael and Meri, Seppo},
  issn         = {1553-7366},
  language     = {eng},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {Yersinia enterocolitica serum resistance proteins YadA and Ail bind the complement regulator C4b-binding protein},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1000140},
  volume       = {4},
  year         = {2008},
}