A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing

•Mammalian epithelial cells produce an autoinducer-2 (AI-2) mimic in response to bacteria•Direct and indirect bacterial contact induces AI-2 mimic production•Bacterial AI-2 receptor LuxP/LsrB detects the AI-2 mimic and activates quorum sensing•Mutagenesis reveals genes required for mimic production and detection

SummaryHost-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.

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