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

Abstract

Summary Host-microbial symbioses are vital to health; nonetheless, little is known about the role cross-kingdom 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 inter-species 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 cross-kingdom signaling and host-bacterial symbioses.

Quorum sensing signal–response systems in Gram-negative bacteria

“…Most recently, mammalian epithelial cells were found to release an AI-2 mimic in response to bacteria or to the disruption of tight junctions. The AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP or LsrB, and it activates quorum sensing-driven gene expression in the bacteria 129 (FIG. 6).…”

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

“…There is also interest in enhancing quorum-sensing-controlled behaviors in beneficial bacteria. For example, bacterial biofilm formation is essential in wastewater treatment and food processing, and, in the context of the microbiome, commensal bacteria play roles in fending off invading pathogens, presumably by relying on quorum-sensing-controlled traits 12,13 . Indeed, anti- and pro-quorum-sensing compounds have been developed and show promise in relevant model systems 14–17 .…”

Biochemical Mechanisms of Pathogen Restriction by Intestinal Bacteria

“…Curiously, AHLs are largely absent in the intestine [48, 49], making the relevance of AHL-mediated quorum sensing in the intestine unclear. Host epithelial cells may also engage bacterial quorum sensing pathways to affect intestinal bacteria, as epithelial cells have been shown to produce a partially functional AI-2 mimic in vitro [50]. …”