Autoinducer-2 functions as both a quorum-sensing and metabolic signal in Escherichia coli.

Authors

Noémie Godrie, Xuanlin Chen, Nicolas Näpflin, Lukas Malfertheiner, Assa Yeroslaviz, Christopher Schubert, Rinho Kim, Christian von Mering, Leanid Laganenka

Published in

Applied and environmental microbiology. Pages e0116026. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

Bacteria integrate diverse environmental signals to coordinate behavior, yet the relationship between nutrient sensing and quorum sensing (QS) remains incompletely understood. Autoinducer-2 (AI-2) is unique among QS signals in that its production is tightly linked to central metabolism, raising fundamental questions about the boundary between metabolic and signaling functions. In Escherichia coli, AI-2 coordinates collective behaviors through the lsr operon, whose expression is controlled not only by the AI-2-responsive repressor LsrR but also by the cAMP receptor protein (CRP), placing it at the intersection of carbon sensing and population-level signaling. While inhibition of lsr expression by PTS sugars was previously established, we show that non-PTS sugars similarly suppress lsr expression through CRP, further decoupling QS activation from cell density and coupling it to carbon source availability. Genomic analysis across Enterobacteriaceae reveals that CRP binding sites in the lsr promoter are broadly conserved, indicating that metabolic modulation of AI-2 signaling is an ancestral regulatory feature. Using a FRET-based biosensor, we further show that AI-2 uptake modulates intracellular cAMP levels similarly to non-PTS carbon transport, suggesting AI-2 may have originally functioned as a nutrient substrate. Additionally, we isolated soil- and phyllosphere-associated bacteria capable of utilizing AI-2 as a sole carbon source. Interestingly, this capacity seems to have evolved independently from the ability to produce and metabolize AI-2 through the LuxS/Lsr pathway. Overall, our findings reveal an underappreciated metabolic basis of AI-2 QS and suggest that, in some species, nutrient utilization and intercellular signaling may have diverged from a common ancestral pathway.IMPORTANCEQuorum sensing allows bacteria to coordinate collective behaviors by detecting secreted signaling molecules, yet the evolutionary origins of these systems remain poorly understood. AI-2, one of the most broadly conserved bacterial signals, is derived from central metabolism and processed by machinery in Escherichia coli that strikingly resembles a sugar utilization system. Here, we show that nutrient availability overrides cell density as the primary determinant of AI-2 responsiveness, that this regulatory logic is conserved among Enterobacteriaceae genomes, and that environmental bacteria can grow on AI-2 as a sole carbon source. These findings reframe AI-2 as a signal embedded within, and potentially evolved from, nutrient-sensing pathways, with direct implications for understanding how byproducts of cellular metabolism can acquire signaling functions.

PMID:
42831622
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

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