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.

Characterization of a thaumarchaeal symbiont that drives incomplete nitrification in the tropical spongeIanthella basta

“…N. ianthellae Ca. N. ianthellae encodes a number of genes containing domains postulated to have an evolutionary origin within the eukaryotes and which are thought to be important for modulating interactions between bacteria and eukaryotic hosts (Callebaut et al, 2000;Lurie-Weinberger et al, 2010;Patterson et al, 2014). Recent metagenomic analyses revealed an abundance of genes encoding such eukaryotic-like proteins (ELPs) in the bacterial symbionts of sponges Reynolds and Thomas, 2016;Díez-Vives et al, 2017), with many of these being expressed (Díez-Vives et al, 2017).…”

Characterization of a thaumarchaeal symbiont that drives incomplete nitrification in the tropical spongeIanthella basta

“…N. bastadiensis to reveal whether it fuels assimilation or 380 heterotrophic growth and/or is used for sequential intracellular generation and oxidation of ammonia (de Boer and Laanbroek, 1989;Burton and Prosser, 2001). which are thought to be important for modulating interactions between bacteria and eukaryotic hosts (Callebaut et al, 2000;Lurie-Weinberger et al, 2010;Patterson et al, 2014). Recent metagenomic analyses revealed an abundance of genes encoding such ELPs in the bacterial symbionts of sponges (Fan et al, 2012;Reynolds and Thomas, 2016;Díez-Vives et al, 2017), with many of these being expressed (Díez-Vives et al, 2017).…”

Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy

“…Patterson and colleagues later identified and characterised two proteins, SaTlp1 and SaTlp2, from S . aureus harbouring TIR-like domains [ 47 ]. In contrast to previously characterised bacterial Tdps, these two proteins were associated with an upregulation of host immune signalling through NFκB activation [ 47 ].…”

“…aureus harbouring TIR-like domains [ 47 ]. In contrast to previously characterised bacterial Tdps, these two proteins were associated with an upregulation of host immune signalling through NFκB activation [ 47 ]. Here, we have characterised the Tdp of a significant tier 1 bioterrorism pathogen.…”