title: A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing.
abstract: Host-microbial symbioses are vital to health; nonetheless, little is known about the role crosskingdom signaling plays in these relationships. In a process called quorum sensing, bacteria communicate with one another using extracellular signal molecules called autoinducers. One autoinducer, AI-2, is proposed to promote interspecies bacterial communication, including in the mammalian gut. We show that mammalian epithelia produce an AI-2 mimic activity in response to bacteria or tight-junction disruption. This AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP/LsrB, and can activate quorum-sensing-controlled gene expression, including in the enteric pathogen Salmonella typhimurium. AI-2 mimic activity is induced when epithelia are directly or indirectly exposed to bacteria, suggesting that a secreted bacterial component(s) stimulates its production. Mutagenesis revealed genes required for bacteria to both detect and stimulate production of the AI-2 mimic. These findings uncover a potential role for the mammalian AI-2 mimic in fostering crosskingdom signaling and host-bacterial symbioses.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544 USA.
authors.forename: Anisa S
authors.initials: AS
authors.lastname: Ismail
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544 USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815 USA.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Valastyan
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544 USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815 USA. Electronic address: bbassler@princeton.edu.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Bassler
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007783:Lactones / Q000378:metabolism*; D053038:Quorum Sensing; D012480:Salmonella Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D006714:Homoserine