title: Cross-Talk betweenStaphylococcus aureusand Other Staphylococcal Species via theagrQuorum Sensing System.
abstract: Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers,Staphylococcus aureusis an opportunistic pathogen capable of causing severe infections.S. aureusvirulence is controlled by theagrquorum sensing system responding to secreted auto-inducing peptides (AIPs) sensed by AgrC, a two component histidine kinase.agrloci are found also in other staphylococcal species and forStaphylococcus epidermidis, the encoded AIP represses expression ofagrregulated virulence genes inS. aureus. In this study we aimed to better understand the interaction between staphylococci andS. aureus, and show that this interaction may eventually lead to the identification of new anti-virulence candidates to targetS. aureusinfections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibitS. aureus agr. The dog pathogen,Staphylococcus schleiferi, expressed the most potent inhibitory activity and was active against all fouragrclasses found inS. aureus. By employing aS. aureusstrain encoding a constitutively active AIP receptor we show that the activity is mediated viaagr. Subsequent cloning and heterologous expression of theS. schleiferiAIP inS. aureusdemonstrated that this molecule was likely responsible for the inhibitory activity, and further proof was provided when pure syntheticS. schleiferiAIP was able to completely abolishagrinduction of anS. aureusreporter strain. To assess impact onS. aureusvirulence, we co-inoculatedS. aureusandS. schleiferi in vivoin theGalleria mellonellawax moth larva, and found that expression of keyS. aureusvirulence factors was abrogated. Our data show that theS. aureus agrlocus is highly responsive to other staphylococcal species suggesting thatagris an inter-species communication system. Based on these results we speculate that interactions betweenS. aureusand other colonizing staphylococci will significantly influence the ability ofS. aureusto cause infection, and we propose that other staphylococci are potential sources of compounds that can be applied as anti-virulence therapy for combatingS. aureusinfections.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen Frederiksberg, Denmark.
authors.forename: Jaime
authors.initials: J
authors.lastname: Canovas
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen Frederiksberg, Denmark.
authors.forename: Mara
authors.initials: M
authors.lastname: Baldry
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen Frederiksberg, Denmark.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Bojer
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of CopenhagenFrederiksberg, Denmark; Department of Microbiology and Infection Control, Statens Serum InstitutCopenhagen, Denmark.
authors.forename: Paal S
authors.initials: PS
authors.lastname: Andersen
authors.affiliation: Center for Biopharmaceuticals and Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Grzeskowiak
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut Copenhagen, Denmark.
authors.forename: Marc
authors.initials: M
authors.lastname: Stegger
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen Frederiksberg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Damborg
authors.affiliation: Center for Biopharmaceuticals and Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Olsen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen Frederiksberg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Ingmer
keywords: Staphylococcus aureus; Staphylococcus schleiferi; agr; anti-virulence therapy; auto-inducing peptide; cross-talk; quorum sensing; quorum sensing inhibition