AUTHOR=Patterson Nicholas J. , Günther Juliane , Gibson Amanda J. , Offord Victoria , Coffey Tracey J. , Splitter Gary , Monk Ian , Seyfert Hans-Martin , Werling Dirk 

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

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 5 - 2014

YEAR=2014

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2014.00662

DOI=10.3389/fmicb.2014.00662

ISSN=1664-302X

ABSTRACT=Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of livestock-associated methicillin-resistant Staphylococcus aureus infections in Europe and North America. This strain is characterised 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) inhibitng 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 the potential for a slightly increased survival rate in a murine infectious model compared to the wild-type strain at one dose, but the data did not reach level of significance. Our data suggest that both proteins may act as factors contributing to the enhanced ability of ST398 to cross species-barriers.