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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1285114
- author
- Kirjavainen, Vesa
; Jarva, Hanna
; Biedzka-Sarek, Marta
; Blom, Anna
LU
; Skurnik, Mikael
and Meri, Seppo
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Pathogens
- volume
- 4
- issue
- 8
- publisher
- Public Library of Science (PLoS)
- 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
- 2016-04-01 12:24:47
- date last changed
- 2022-01-27 03:21:59
@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 (PLoS)}},
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}},
doi = {{10.1371/journal.ppat.1000140}},
volume = {{4}},
year = {{2008}},
}