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The TLR2 Antagonist Staphylococcal Superantigen-Like Protein 3 Acts as a Virulence Factor to Promote Bacterial Pathogenicity in vivo

Koymans, Kirsten J ; Goldmann, Oliver ; Karlsson, Christofer A Q LU ; Sital, Wiedjai ; Thänert, Robert ; Bisschop, Adinda ; Vrieling, Manouk ; Malmström, Johan LU orcid ; Kessel, Kok P.M. and de Haas, Carla J C , et al. (2017) In Journal of Innate Immunity 9. p.561-573
Abstract

Toll-like receptor (TLR) signaling is important in the initiation of immune responses and subsequent instigation of adaptive immunity. TLR2 recognizes bacterial lipoproteins and plays a central role in the host defense against bacterial infections, including those caused by Staphylococcus aureus. Many studies have demonstrated the importance of TLR2 in murine S. aureus infection. S. aureus evades TLR2 activation by secreting two proteins, staphylococcal superantigen-like protein 3 (SSL3) and 4 (SSL4). In this study, we demonstrate that antibodies against SSL3 and SSL4 are found in healthy individuals, indicating that humans are exposed to these proteins during S. aureus colonization or infection. To investigate the TLR2-antagonistic... (More)

Toll-like receptor (TLR) signaling is important in the initiation of immune responses and subsequent instigation of adaptive immunity. TLR2 recognizes bacterial lipoproteins and plays a central role in the host defense against bacterial infections, including those caused by Staphylococcus aureus. Many studies have demonstrated the importance of TLR2 in murine S. aureus infection. S. aureus evades TLR2 activation by secreting two proteins, staphylococcal superantigen-like protein 3 (SSL3) and 4 (SSL4). In this study, we demonstrate that antibodies against SSL3 and SSL4 are found in healthy individuals, indicating that humans are exposed to these proteins during S. aureus colonization or infection. To investigate the TLR2-antagonistic properties of SSL3 and SSL4, we compared the infection with wild-type and SSL3/4 knockout S. aureus strains in an intravenous murine infection model. Direct evaluation of the contribution of SSL3/4 to infection pathogenesis was hindered by the fact that the SSLs were not expressed in the murine system. To circumvent this limitation, an SSL3-overproducing strain (pLukM-SSL3) was generated, resulting in constitutive expression of SSL3. pLukM-SSL3 exhibited increased virulence compared to the parental strain in a murine model that was found to be TLR2 dependent. Altogether, these data indicate that SSL3 contributes to S. aureus virulence in vivo.

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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Innate Immunity
volume
9
pages
561 - 573
publisher
Karger
external identifiers
  • scopus:85028769711
  • wos:000416161900004
  • pmid:28858870
ISSN
1662-811X
DOI
10.1159/000479100
language
English
LU publication?
yes
id
800918f8-71ce-4b94-b60c-0319c41db9d9
date added to LUP
2017-09-04 17:09:58
date last changed
2024-03-31 14:22:49
@article{800918f8-71ce-4b94-b60c-0319c41db9d9,
  abstract     = {{<p>Toll-like receptor (TLR) signaling is important in the initiation of immune responses and subsequent instigation of adaptive immunity. TLR2 recognizes bacterial lipoproteins and plays a central role in the host defense against bacterial infections, including those caused by Staphylococcus aureus. Many studies have demonstrated the importance of TLR2 in murine S. aureus infection. S. aureus evades TLR2 activation by secreting two proteins, staphylococcal superantigen-like protein 3 (SSL3) and 4 (SSL4). In this study, we demonstrate that antibodies against SSL3 and SSL4 are found in healthy individuals, indicating that humans are exposed to these proteins during S. aureus colonization or infection. To investigate the TLR2-antagonistic properties of SSL3 and SSL4, we compared the infection with wild-type and SSL3/4 knockout S. aureus strains in an intravenous murine infection model. Direct evaluation of the contribution of SSL3/4 to infection pathogenesis was hindered by the fact that the SSLs were not expressed in the murine system. To circumvent this limitation, an SSL3-overproducing strain (pLukM-SSL3) was generated, resulting in constitutive expression of SSL3. pLukM-SSL3 exhibited increased virulence compared to the parental strain in a murine model that was found to be TLR2 dependent. Altogether, these data indicate that SSL3 contributes to S. aureus virulence in vivo.</p>}},
  author       = {{Koymans, Kirsten J and Goldmann, Oliver and Karlsson, Christofer A Q and Sital, Wiedjai and Thänert, Robert and Bisschop, Adinda and Vrieling, Manouk and Malmström, Johan and Kessel, Kok P.M. and de Haas, Carla J C and van Strijp, Jos A.G. and Medina, Eva}},
  issn         = {{1662-811X}},
  language     = {{eng}},
  month        = {{09}},
  pages        = {{561--573}},
  publisher    = {{Karger}},
  series       = {{Journal of Innate Immunity}},
  title        = {{The TLR2 Antagonist Staphylococcal Superantigen-Like Protein 3 Acts as a Virulence Factor to Promote Bacterial Pathogenicity in vivo}},
  url          = {{http://dx.doi.org/10.1159/000479100}},
  doi          = {{10.1159/000479100}},
  volume       = {{9}},
  year         = {{2017}},
}