Two TIR-like domain containing proteins in a newly emerging zoonotic Staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response
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 tr...
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doaj-fbd129d6a2fc424ebc0037f4917c435a2020-11-25T00:18:25ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2014-12-01510.3389/fmicb.2014.00662106040Two TIR-like domain containing proteins in a newly emerging zoonotic Staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune responseNicholas J Patterson0Juliane eGuenther1Amanda Jane Gibson2Victoria eOfford3Tracey J Coffey4Gary eSplitter5Ian eMonk6Hans-Martin eSeyfert7Dirk eWerling8Royal Veterinary CollegeLeibniz-Institute for Farm Animal BiologyRoyal Veterinary CollegeRoyal Veterinary CollegeFaculty of Medicine and Health SciencesUniversity of Wisconsin-MadisonUniversity of Melbourne, Faculty of Medicine, Dentistry and Health SciencesLeibniz-Institute for Farm Animal BiologyRoyal Veterinary CollegeStaphylococcus 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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00662/fullBacterial Proteinsmouse modelinnate immune responseTCPTLR signalingS.aureus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicholas J Patterson Juliane eGuenther Amanda Jane Gibson Victoria eOfford Tracey J Coffey Gary eSplitter Ian eMonk Hans-Martin eSeyfert Dirk eWerling |
spellingShingle |
Nicholas J Patterson Juliane eGuenther Amanda Jane Gibson Victoria eOfford Tracey J Coffey Gary eSplitter Ian eMonk Hans-Martin eSeyfert Dirk eWerling Two TIR-like domain containing proteins in a newly emerging zoonotic Staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response Frontiers in Microbiology Bacterial Proteins mouse model innate immune response TCP TLR signaling S.aureus |
author_facet |
Nicholas J Patterson Juliane eGuenther Amanda Jane Gibson Victoria eOfford Tracey J Coffey Gary eSplitter Ian eMonk Hans-Martin eSeyfert Dirk eWerling |
author_sort |
Nicholas J Patterson |
title |
Two TIR-like domain containing proteins in a newly emerging zoonotic Staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response |
title_short |
Two TIR-like domain containing proteins in a newly emerging zoonotic Staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response |
title_full |
Two TIR-like domain containing proteins in a newly emerging zoonotic Staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response |
title_fullStr |
Two TIR-like domain containing proteins in a newly emerging zoonotic Staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response |
title_full_unstemmed |
Two TIR-like domain containing proteins in a newly emerging zoonotic Staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response |
title_sort |
two tir-like domain containing proteins in a newly emerging zoonotic staphyloccoccus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2014-12-01 |
description |
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. |
topic |
Bacterial Proteins mouse model innate immune response TCP TLR signaling S.aureus |
url |
http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00662/full |
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