biostudies-literatureShine EELife Sciences Research FoundationHoward Hughes Medical InstituteNational Institutes of Health (NIH)National Science Foundation (NSF)6258-6269https://www.ebi.ac.uk/biostudies/studies/S-EPMC12921845biostudies-literatureUnknown148(6)Bacteria use small molecules to orchestrate collective behaviors in a process called quorum sensing (QS), which relies on the production, release, and group-wide detection of extracellular signal molecules referred to as autoinducers. One QS autoinducer, termed AI-2, is broadly used for interspecies bacterial communication, including in the mammalian gut. AI-2 consists of a family of interconverting compounds and adducts originating from 4,5-dihydroxy-2,3-pentanedione. This complex speciation, coupled with the inherent instability of AI-2 congeners, have complicated isolation efforts. It has been known that mammalian epithelial cells produce an AI-2 mimic to which bacteria respond. However, the identity of the AI-2 mimic has remained elusive, presumably due to its instability, similar to tJournal of the American Chemical SocietyDiscovery of a Human Metabolite That Mimics the Bacterial Quorum-Sensing Autoinducer AI-2.PMC12921845R21AT013123MCB-2508324R37GM065859Huang JZShine EEValastyan JSSeyedsayamdost MRYing VYBassler BLfalseDiscovery of a Human Metabolite That Mimics the Bacterial Quorum-Sensing Autoinducer AI-2.Bacteria use small molecules to orchestrate collective behaviors in a process called quorum sensing (QS), which relies on the production, release, and group-wide detection of extracellular signal molecules referred to as autoinducers. One QS autoinducer, termed AI-2, is broadly used for interspecies bacterial communication, including in the mammalian gut. AI-2 consists of a family of interconverting compounds and adducts originating from 4,5-dihydroxy-2,3-pentanedione. This complex speciation, coupled with the inherent instability of AI-2 congeners, have complicated isolation efforts. It has been known that mammalian epithelial cells produce an AI-2 mimic to which bacteria respond. However, the identity of the AI-2 mimic has remained elusive, presumably due to its instability, similar to t2026-01-01T00:00:00Z2026 Feb2026-07-16T15:11:40.896Z2026-07-09T11:03:47.359ZS-EPMC129218454163870910.1021/jacs.5c18527