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

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