title: 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.
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.
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College Hatfield, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Patterson
authors.affiliation: Leibniz Institute for Farm Animal Biology Dummerstorf, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Günther
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College Hatfield, UK.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Gibson
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College Hatfield, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Offord
authors.affiliation: School of Veterinary Medicine and Sciences, Faculty of Medicine and Health Sciences, University of Nottingham Sutton Bonington, UK.
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Coffey
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison Madison, WI, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Splitter
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne Melbourne, VIC, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Monk
authors.affiliation: Leibniz Institute for Farm Animal Biology Dummerstorf, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Seyfert
authors.affiliation: Molecular Immunology Group, Department of Pathology and Pathogen Biology, Royal Veterinary College Hatfield, UK.
authors.forename: Dirk
authors.initials: D
authors.lastname: Werling
keywords: Staphylococcus aureus; TCP; TLR signaling; bacterial proteins; innate immune response; mouse model