title: The Yersinia pseudotuberculosis outer membrane protein Ail recruits the human complement regulatory protein factor H.
abstract: Previous investigations characterizing the mechanism(s) of complement resistance in Yersinia pseudotuberculosis showed that the outer membrane protein Ail can functionally recruit the regulator of the classical and lectin pathways of complement, C4b-binding protein. In this study, we extend these observations and show that Ail can also recruit the regulator of the alternative pathway (AP), factor H (fH). Binding to fH was dependent on Ail expression and observed in the context of full-length LPS. Inactivation of ail resulted in loss of fH binding. Ail expression conferred resistance to AP-mediated killing. Bound fH was functional as a cofactor for factor I-mediated cleavage and inactivation of C3b. Ail alone is sufficient to mediate fH binding and resistance to AP-mediated killing, because Ail expression in a laboratory Escherichia coli strain conferred both of these phenotypes. Binding was specific and inhibited by increasing heparin and NaCl concentrations. Using a panel of fH recombinant fragments, we observed that both short consensus repeats 5-7 and 19-20 regions are responsible for mediating the interaction with Ail. Collectively, these results suggest that fH recruitment is an additional mechanism of complement resistance of Ail. Recruitment of both fH and C4BP by Ail may confer Y. pseudotuberculosis with the ability to resist all pathways of complement activation.
authors.affiliation: Infection Biology Program, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, FIN-00014 Helsinki, Finland. derek.ho@helsinki.fi
authors.forename: Derek K
authors.initials: DK
authors.lastname: Ho
authors.forename: Rauna
authors.initials: R
authors.lastname: Riva
authors.forename: Mikael
authors.initials: M
authors.lastname: Skurnik
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D001770:Blood Bactericidal Activity / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D017242:Complement Factor H / Q000378:metabolism*; D060467:Disease Resistance / Q000276:immunology; D006801:Humans; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D015011:Yersinia pseudotuberculosis / Q000276:immunology*
chemical_list: C576634:Ail protein, Yersinia pseudotuberculosis; D001053:Apolipoproteins; D001425:Bacterial Outer Membrane Proteins; C105092:CFHR4 protein, human; D017242:Complement Factor H