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

Mühlenkamp, Melanie C.; Hallström, Teresia LU ; Autenrieth, Ingo B.; Bohn, Erwin; Linke, Dirk; Rinker, Janina; Riesbeck, Kristian LU ; Singh, Birendra; Leo, Jack C. and Hammerschmidt, Sven, et al. (2017) In Journal of Innate Immunity 9(1). p.33-51
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.... (More)

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.

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published
subject
keywords
<italic>Yersinia</italic> adhesin A, Bacterial infection, Cell surface molecules, Complement, Vitronectin
in
Journal of Innate Immunity
volume
9
issue
1
pages
33 - 51
publisher
Karger
external identifiers
  • scopus:84994173337
  • wos:000392166700005
ISSN
1662-811X
DOI
10.1159/000449200
language
English
LU publication?
yes
id
aa839271-ae36-45cc-9178-dce3ca77f6ac
date added to LUP
2016-11-21 11:22:33
date last changed
2018-01-07 11:36:05
@article{aa839271-ae36-45cc-9178-dce3ca77f6ac,
  abstract     = {<p>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.</p>},
  author       = {Mühlenkamp, Melanie C. and Hallström, Teresia and Autenrieth, Ingo B. and Bohn, Erwin and Linke, Dirk and Rinker, Janina and Riesbeck, Kristian and Singh, Birendra and Leo, Jack C. and Hammerschmidt, Sven and Zipfel, Peter F. and Schütz, Monika S.},
  issn         = {1662-811X},
  keyword      = {<italic>Yersinia</italic> adhesin A,Bacterial infection,Cell surface molecules,Complement,Vitronectin},
  language     = {eng},
  number       = {1},
  pages        = {33--51},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {Vitronectin Binds to a Specific Stretch within the Head Region of Yersinia Adhesin A and Thereby Modulates Yersinia enterocolitica Host Interaction},
  url          = {http://dx.doi.org/10.1159/000449200},
  volume       = {9},
  year         = {2017},
}