AUTHOR=Canovas Jaime , Baldry Mara , Bojer Martin S. , Andersen Paal S. , Gless Bengt H. , Grzeskowiak Piotr K. , Stegger Marc , Damborg Peter , Olsen Christian A. , Ingmer Hanne 

TITLE=Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the agr Quorum Sensing System

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01733

DOI=10.3389/fmicb.2016.01733

ISSN=1664-302X

ABSTRACT=<p>Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers, <italic>Staphylococcus aureus</italic> is an opportunistic pathogen capable of causing severe infections. <italic>S. aureus</italic> virulence is controlled by the <italic>agr</italic> quorum sensing system responding to secreted auto-inducing peptides (AIPs) sensed by AgrC, a two component histidine kinase. <italic>agr</italic> loci are found also in other staphylococcal species and for <italic>Staphylococcus epidermidis</italic>, the encoded AIP represses expression of <italic>agr</italic> regulated virulence genes in <italic>S. aureus</italic>. In this study we aimed to better understand the interaction between staphylococci and <italic>S. aureus</italic>, and show that this interaction may eventually lead to the identification of new anti-virulence candidates to target <italic>S. aureus</italic> infections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibit <italic>S. aureus agr</italic>. The dog pathogen, <italic>Staphylococcus schleiferi</italic>, expressed the most potent inhibitory activity and was active against all four <italic>agr</italic> classes found in <italic>S. aureus</italic>. By employing a <italic>S. aureus</italic> strain encoding a constitutively active AIP receptor we show that the activity is mediated via <italic>agr</italic>. Subsequent cloning and heterologous expression of the <italic>S. schleiferi</italic> AIP in <italic>S. aureus</italic> demonstrated that this molecule was likely responsible for the inhibitory activity, and further proof was provided when pure synthetic <italic>S. schleiferi</italic> AIP was able to completely abolish <italic>agr</italic> induction of an <italic>S. aureus</italic> reporter strain. To assess impact on <italic>S. aureus</italic> virulence, we co-inoculated <italic>S. aureus</italic> and <italic>S. schleiferi in vivo</italic> in the <italic>Galleria mellonella</italic> wax moth larva, and found that expression of key <italic>S. aureus</italic> virulence factors was abrogated. Our data show that the <italic>S. aureus agr</italic> locus is highly responsive to other staphylococcal species suggesting that <italic>agr</italic> is an inter-species communication system. Based on these results we speculate that interactions between <italic>S. aureus</italic> and other colonizing staphylococci will significantly influence the ability of <italic>S. aureus</italic> to cause infection, and we propose that other staphylococci are potential sources of compounds that can be applied as anti-virulence therapy for combating <italic>S. aureus</italic> infections.</p>