https://phaidra.vetmeduni.ac.at/o:2504 Cross-species communication via agr controls phage susceptibility in Staphylococcus aureus Yang, Jingxian Jingxian Yang University of Copenhagen Ingmer, Hanne Hanne Ingmer University of Copenhagen Peschel, Andreas Andreas Peschel University of Tübingen / German Center for Infection Research Grunert, Tom Tom Grunert 0000-0001-5722-6631 University of Veterinary Medicine Vienna Bojer, Martin Saxtorph Martin Saxtorph Bojer University of Copenhagen Silva, Stephanie Fulaz Stephanie Fulaz Silva University of Copenhagen Bowring, Janine Zara Janine Zara Bowring University of Copenhagen Krusche, Janes Janes Krusche University of Tübingen / German Center for Infection Research Lehmann, Esther Esther Lehmann University of Copenhagen Bejder, Benjamin Svejdal Benjamin Svejdal Bejder University of Copenhagen Cell Press text eng 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:2504/download 10.1016/j.celrep.2023.113154 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Cell reports 42(9) (2023) Cell reports 42 9 3.56 MB 2023