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Yersinia enterocolitica YadA mediates complement evasion by recruitment and inactivation of C3 products.

Authors
  • Schindler, Magnus K H
  • Schütz, Monika S
  • Mühlenkamp, Melanie C
  • Rooijakkers, Suzan H M
  • Hallström, Teresia
  • Zipfel, Peter F
  • Autenrieth, Ingo B
Type
Published Article
Journal
The Journal of Immunology
Publisher
The American Association of Immunologists
Publication Date
Nov 15, 2012
Volume
189
Issue
10
Pages
4900–4908
Identifiers
DOI: 10.4049/jimmunol.1201383
PMID: 23071281
Source
Medline
License
Unknown

Abstract

Yersinia adhesin A (YadA) is a major virulence factor of Yersinia enterocolitica. YadA mediates host cell binding and autoaggregation and protects the pathogen from killing by the complement system. Previous studies demonstrated that YadA is the most important single factor mediating serum resistance of Y. enterocolitica, presumably by binding C4b binding protein (C4BP) and factor H, which are both complement inhibitors. Factor H acts as a cofactor for factor I-mediated cleavage of C3b into the inactive form iC3b and thus prevents formation of inflammatory effector compounds and the terminal complement complex. In this study, we challenged the current direct binding model of factor H to YadA and show that Y. enterocolitica YadA recruits C3b and iC3b directly, without the need of an active complement cascade or additional serum factors. Enhanced binding of C3b does not decrease survival of YadA-expressing Yersiniae because C3b becomes readily inactivated by factor H and factor I. Binding of factor H to YadA is greatly reduced in the absence of C3. Experiments using Yersinia lacking YadA or expressing YadA with reduced trimeric stability clearly demonstrate that both the presence and full trimeric stability of YadA are essential for complement resistance. A novel mechanism of factor H binding is presented in which YadA exploits recruitment of C3b or iC3b to attract large amounts of factor H. As a consequence, formation of the terminal complement complex is limited and bacterial survival is enhanced. These findings add a new aspect of how Y. enterocolitica effectively evades the host complement system.

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