Study reveals autoinducer-2 functions as both quorum sensing signal and metabolic nutrient in bacteria
A new preprint study published on bioRxiv demonstrates that the bacterial quorum sensing molecule Autoinducer-2 (AI-2) functions as both a metabolic nutrient signal and a population-density signal in E. coli, with its expression suppressed by carbon source availability rather than cell density alone. The research shows that CRP, a carbon-sensing protein, regulates the AI-2 signaling pathway across many Enterobacteriaceae species, and that some environmental bacteria can use AI-2 as a sole carbon source. These findings suggest that AI-2's role as a quorum sensing signal may have evolved from an ancestral function as a metabolic substrate, blurring the line between nutrient sensing and collective bacterial behavior.
Researchers report in a bioRxiv preprint that Autoinducer-2 (AI-2), a widely studied bacterial quorum sensing (QS) molecule in Escherichia coli, operates at the intersection of carbon metabolism and population-level signaling. The study shows that both PTS sugars like glucose and non-PTS sugars suppress expression of the lsr operon — the genetic pathway responsible for AI-2 uptake and response — through the cAMP receptor protein (CRP), meaning QS activation is coupled to carbon source availability rather than cell density alone. Using a FRET-based biosensor, the team found that AI-2 uptake modulates intracellular cAMP levels in a manner similar to non-PTS carbon source transport, suggesting the molecule is processed metabolically. Genomic analysis of Enterobacteriaceae revealed that CRP binding sites in the lsr promoter region are broadly conserved across the family, indicating this metabolic regulation is an ancestral feature rather than a recent adaptation. Critically, the researchers isolated soil- and phyllosphere-associated bacteria capable of growing on AI-2 as a sole carbon source, providing direct evidence that the molecule can serve a nutritional role. Taken together, the findings support an evolutionary hypothesis in which AI-2 signaling emerged from, or co-evolved with, ancestral carbon utilization pathways, challenging the conventional view of AI-2 as a dedicated quorum sensing signal.
What's missing
As a preprint, this study has not yet undergone formal peer review, so findings should be interpreted with caution. The study does not fully resolve whether AI-2's metabolic and signaling roles are separable at the mechanistic level, nor does it quantify the relative contribution of each function under natural environmental conditions. The evolutionary timeline proposed — that signaling emerged from nutrient utilization — remains a hypothesis supported by correlational and genomic evidence rather than direct experimental reconstruction of ancestral pathways.
What different sources said
- bioRxivCenter
Autoinducer-2 functions as both a quorum sensing and metabolic signal in Escherichia coli
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