Cross-species communication via agr controls phage susceptibility in Staphylococcus aureus
Jingxian Yang,
Janine Zara Bowring,
Janes Krusche,
Esther Lehmann,
Benjamin Svejdal Bejder,
Stephanie Fulaz Silva,
Martin Saxtorph Bojer,
Tom Grunert,
Andreas Peschel,
Hanne Ingmer
Affiliations
Jingxian Yang
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Copenhagen, Denmark
Janine Zara Bowring
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Copenhagen, Denmark
Janes Krusche
Department of Infection Biology, Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI),” German Center for Infection Research (DZIF), Tübingen, Germany
Esther Lehmann
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Copenhagen, Denmark
Benjamin Svejdal Bejder
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
Stephanie Fulaz Silva
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Copenhagen, Denmark
Martin Saxtorph Bojer
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Copenhagen, Denmark
Tom Grunert
Functional Microbiology, Institute of Microbiology, Department of Pathobiology, University of Veterinary Medicine, 1210 Vienna, Austria
Andreas Peschel
Department of Infection Biology, Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, 72076 Tübingen, Germany; Cluster of Excellence “Controlling Microbes to Fight Infections (CMFI),” German Center for Infection Research (DZIF), Tübingen, Germany
Hanne Ingmer
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Copenhagen, Denmark; Corresponding author
Summary: Bacteria use quorum sensing (QS) to coordinate group behavior in response to cell density, and some bacterial viruses (phages) also respond to QS. In Staphylococcus aureus, the agr-encoded QS system relies on accumulation of auto-inducing cyclic peptides (AIPs). Other staphylococci also produce AIPs of which many inhibit S. aureus agr. We show that agr induction reduces expression of tarM, encoding a glycosyltransferase responsible for α-N-acetylglucosamine modification of the major S. aureus phage receptor, the wall teichoic acids. This allows lytic phage Stab20 and related phages to infect and kill S. aureus. However, in mixed communities, producers of inhibitory AIPs like S. haemolyticus, S. caprae, and S. pseudintermedius inhibit S. aureus agr, thereby impeding phage infection. Our results demonstrate that cross-species interactions dramatically impact phage susceptibility. These interactions likely influence microbial ecology and impact the efficacy of phages in medical and biotechnological applications such as phage therapy.
