IAI Accepts, published online ahead of print on 14 July 2008

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Infect. Immun. doi:10.1128/IAI.00313-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Characterization of complement factor H binding to Yersinia enterocolitica serotype O:3

Marta Biedzka-Sarek, Hanna Jarva, Heidi Hyytiäinen, Seppo Meri, and Mikael Skurnik^*

Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland; and Helsinki University Central Hospital Laboratory Diagnostics, Helsinki, Finland

^* To whom correspondence should be addressed. Email: mikael.skurnik{at}helsinki.fi.

A number of bacteria bind factor H (FH), the negative regulator of the alternative complement pathway, to avoid complement-mediated killing. Here we show that a gram-negative enteric pathogen Yersinia enterocolitica serotype O:3 uses two virulence-related outer membrane (OM) proteins to bind FH. Using Y. enterocolitica O:3 mutant strains, displaying different combinations of surface factors relevant to complement resistance, we demonstrated that the major receptor for FH is the OM protein YadA. Another OM protein, Ail, also contributes to FH-binding provided that it is not blocked by distal parts of the lipopolysaccharide (i.e., the O-antigen and the outer core hexasaccharide). Importantly, we demonstrated that surface-bound FH was functional; both YadA- and Ail-bound FH displayed cofactor activity for factor I -mediated cleavage of C3b. Using truncated recombinant FH constructs we located the binding site of Ail specifically to short consensus repeats (SCRs) 6 and 7 of FH, while YadA showed a novel type of FH-binding pattern and appears to bind FH throughout the entire FH molecule. We thus conclude that Y. enterocolitica, via YadA and Ail, recruits functionally active FH to its surface. FH-binding appears to be an important mechanism of the complement resistance of this pathogen.

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• Biedzka-Sarek, M., Salmenlinna, S., Gruber, M., Lupas, A. N., Meri, S., Skurnik, M. (2008). Functional Mapping of YadA- and Ail-Mediated Binding of Human Factor H to Yersinia enterocolitica Serotype O:3. Infect. Immun. 76: 5016-5027 [Abstract] [Full Text]