title: Vitronectin Binds to a Specific Stretch within the Head Region of Yersinia Adhesin A and Thereby Modulates Yersinia enterocolitica Host Interaction.
abstract: Complement resistance is an important virulence trait of Yersinia enterocolitica (Ye). The predominant virulence factor expressed by Ye is Yersinia adhesin A (YadA), which enables bacterial attachment to host cells and extracellular matrix and additionally allows the acquisition of soluble serum factors. The serum glycoprotein vitronectin (Vn) acts as an inhibitory regulator of the terminal complement complex by inhibiting the lytic pore formation. Here, we show YadA-mediated direct interaction of Ye with Vn and investigated the role of this Vn binding during mouse infection in vivo. Using different Yersinia strains, we identified a short stretch in the YadA head domain of Ye O:9 E40, similar to the 'uptake region' of Y. pseudotuberculosis YPIII YadA, as crucial for efficient Vn binding. Using recombinant fragments of Vn, we found the C-terminal part of Vn, including heparin-binding domain 3, to be responsible for binding to YadA. Moreover, we found that Vn bound to the bacterial surface is still functionally active and thus inhibits C5b-9 formation. In a mouse infection model, we demonstrate that Vn reduces complement-mediated killing of Ye O:9 E40 and, thus, improved bacterial survival. Taken together, these findings show that YadA-mediated Vn binding influences Ye pathogenesis.
authors: Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, Germany.
authors: Melanie C
authors: MC
authors: Mühlenkamp
authors: Teresia
authors: T
authors: Hallström
authors: Ingo B
authors: IB
authors: Autenrieth
authors: Erwin
authors: E
authors: Bohn
authors: Dirk
authors: D
authors: Linke
authors: Janina
authors: J
authors: Rinker
authors: Kristian
authors: K
authors: Riesbeck
authors: Birendra
authors: B
authors: Singh
authors: Jack C
authors: JC
authors: Leo
authors: Sven
authors: S
authors: Hammerschmidt
authors: Peter F
authors: PF
authors: Zipfel
authors: Monika S
authors: MS
authors: Schütz
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D001433:Bacteriolysis; D003165:Complement System Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D000072417:Protein Domains / Q000235:genetics; D013045:Species Specificity; D014774:Virulence; D019096:Vitronectin / Q000235:genetics / Q000378:metabolism*; D015009:Yersinia Infections / Q000276:immunology*; D015008:Yersinia enterocolitica / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D019096:Vitronectin; C064832:YadA protein, Yersinia; D003165:Complement System Proteins