o:2504 Cross-species communication via agr controls phage susceptibility in Staphylococcus aureus en 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. Humans; Staphylococcus aureusmetabolism; Bacteriophagesmetabolism; Staphylococcusmetabolism; Glycosyltransferasesmetabolism; Staphylococcal Infections; Bacterial Proteinsmetabolism; Quorum Sensing 1552099 10.1016/j.celrep.2023.113154 2024-02-08T09:41:00.988Z 44 yes 46 Jingxian Yang University of Copenhagen Janine Zara Bowring University of Copenhagen person Janes Krusche University of Tübingen / German Center for Infection Research person Esther Lehmann University of Copenhagen person Benjamin Svejdal Bejder University of Copenhagen person Stephanie Fulaz Silva University of Copenhagen person Martin Saxtorph Bojer University of Copenhagen person Tom Grunert University of Veterinary Medicine Vienna person 0000-0001-5722-6631 Andreas Peschel University of Tübingen / German Center for Infection Research person Hanne Ingmer University of Copenhagen person application/pdf 3734968 https://phaidra.vetmeduni.ac.at/o:2504 no yes 18 70 1552253 Cell reports 13 42 9 Cell Press 2023