Two TIR-like domain containing proteins in a newly emerging zoonotic Staphylococcus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response

Authors Organisations
  • Nicholas J. Patterson(Author)
    Royal Veterinary College
  • Juliane Günther(Author)
    Leibniz Institute for Farm Animal Biology
  • Amanda Gibson(Author)
    Royal Veterinary College
  • Victoria Offord(Author)
    Royal Veterinary College
  • Tracey J. Coffey(Author)
    University of Nottingham
  • Gary Splitter(Author)
    University of Wisconsin-Madison
  • Ian Monk(Author)
    The University of Melbourne
  • Hans-martin Seyfert(Author)
    Leibniz Institute for Farm Animal Biology
  • Dirk Werling(Author)
    Royal Veterinary College
Type Article
Original languageEnglish
Article number662
Number of pages14
JournalFrontiers in Microbiology
Volume5
DOI
Publication statusPublished - 09 Dec 2014
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Abstract

Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of livestock-associated methicillin-resistant S. aureus infections in Europe and North America. This strain is characterized by high promiscuity in terms of host-species and also lacks several traditional S. aureus virulence factors. This does not, however, explain the apparent ease with which it crosses species-barriers. Recently, TIR-domain containing proteins (Tcps) which inhibit the innate immune response were identified in some Gram-negative bacteria. Here we report the presence of two proteins, S. aureus TIR-like Protein 1 (SaTlp1) and S. aureus TIR-like Protein 2 (SaTlp2), expressed by ST398 which contain domain of unknown function 1863 (DUF1863), similar to the Toll/IL-1 receptor (TIR) domain. In contrast to the Tcps in Gram-negative bacteria, our data suggest that SaTlp1 and SaTlp2 increase activation of the transcription factor NF-κB as well as downstream pro-inflammatory cytokines and immune effectors. To assess the role of both proteins as potential virulence factors knock-out mutants were created. These showed a slightly enhanced survival rate in a murine infectious model compared to the wild-type strain at one dose. Our data suggest that both proteins may act as factors contributing to the enhanced ability of ST398 to cross species-barriers.

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