Vitronectin Binds to a Specific Stretch within the Head Region of Yersinia Adhesin A and Thereby Modulates Yersinia enterocolitica Host Interaction

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.

Hallström, TeresiaLeibniz Institute for Natural Product Research and Infection Biology(Swepub:lu)mikr-tha (författare)
Autenrieth, Ingo B.University Hospital of Tubingen (författare)
Bohn, ErwinUniversity Hospital of Tubingen (författare)
Linke, DirkUniversity of Oslo (författare)
Rinker, JaninaUniversity Hospital of Tubingen (författare)
Riesbeck, KristianLund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups(Swepub:lu)mikr-kri (författare)
Singh, BirendraUniversity of Greifswald (författare)
Leo, Jack C.University of Oslo (författare)
Hammerschmidt, SvenUniversity of Greifswald (författare)
Zipfel, Peter F.Leibniz Institute for Natural Product Research and Infection Biology (författare)
Schütz, Monika S.University Hospital of Tubingen (författare)
University Hospital of TubingenLeibniz Institute for Natural Product Research and Infection Biology (creator_code:org_t)

Av författaren/redakt...: Mühlenkamp, Mela ...; Hallström, Teres ...; Autenrieth, Ingo ...; Bohn, Erwin; Linke, Dirk; Rinker, Janina; visa fler...; Riesbeck, Kristi ...; Singh, Birendra; Leo, Jack C.; Hammerschmidt, S ...; Zipfel, Peter F.; Schütz, Monika S ...; visa färre...

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