Yang, Jingxian (University of Copenhagen) Jingxian Yang Ingmer, Hanne (University of Copenhagen) Hanne Ingmer Peschel, Andreas (University of Tübingen / German Center for Infection Research) Andreas Peschel Grunert, Tom (University of Veterinary Medicine Vienna) Tom Grunert Bojer, Martin Saxtorph (University of Copenhagen) Martin Saxtorph Bojer Silva, Stephanie Fulaz (University of Copenhagen) Stephanie Fulaz Silva Bowring, Janine Zara (University of Copenhagen) Janine Zara Bowring Krusche, Janes (University of Tübingen / German Center for Infection Research) Janes Krusche Lehmann, Esther (University of Copenhagen) Esther Lehmann Bejder, Benjamin Svejdal (University of Copenhagen) Benjamin Svejdal Bejder Cell Press 2023 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. PDFDocument en 2024-02-08T09:41:00.988Z Humans; Staphylococcus aureusmetabolism; Bacteriophagesmetabolism; Staphylococcusmetabolism; Glycosyltransferasesmetabolism; Staphylococcal Infections; Bacterial Proteinsmetabolism; Quorum Sensing 3734968 b application/pdf CC BY-NC-ND 4.0 International