Interplay between chemotaxis, quorum sensing, and metabolism regulates Escherichia coli - Salmonella Typhimurium interactions in vivo

Motile bacteria use chemotaxis to navigate complex environments like the mammalian gut. These bacteria sense a range of chemoeffector molecules, which can either be of nutritional value or provide a cue for the niche best suited for their survival and growth. One such cue molecule is the intra- and interspecies quorum sensing signaling molecule, autoinducer-2 (AI-2). Apart from controlling collective behavior of Escherichia coli , chemotaxis towards AI-2 contributes to its ability to colonize the murine gut. However, the impact of AI-2-dependent niche occupation by E. coli on interspecies interactions in vivo is not fully understood.

Here, using the C57BL/6J mouse infection model, we show that chemotaxis towards AI-2 contributes to nutrient competition and thereby affects colonization resistance conferred by E. coli against the enteric pathogen Salmonella enterica serovar Typhimurium ( S. Tm). Like E. coli , S. Tm also relies on chemotaxis, albeit not towards AI-2, to compete against residing E. coli in a gut inflammation-dependent manner. Finally, by using a barcoded mutant library pool of S. Tm, we analyzed how AI-2 signaling in E. coli affects the central metabolism of S. Tm. AI-2-dependent niche colonization by E. coli specifically affected the fitness of S. Tm mutants deficient in fumarate respiration (Δ dcuABC ) or mannose (Δ manA ) utilization. Our findings thus provide important insights into AI-2-mediated E. coli - S. Tm interactions during gut infection.

Author Summary

Both chemotaxis and AI-2 quorum sensing systems have been extensively studied in Escherichia coli . Despite our understanding of these systems at a molecular level in vitro , their physiological relevance in vivo , particularly in the context of mammalian gut colonization, remains less explored. Building on our previous work on the role of chemotaxis and AI-2 signaling in E. coli gut colonization, we investigated their roles in interspecies interactions. Specifically, we examined how AI-2-dependent colonization by E. coli affects its competition with the enteric pathogen Salmonella enterica serovar Typhimurium ( S. Tm) and the metabolic requirements for S. Tm growth.

Our data show that AI-2 signaling contributes to colonization resistance of E. coli against S. Tm. Although S. Tm also requires chemotaxis to grow efficiently in E. coli -colonized mice, this is independent of its ability to sense AI-2. Notably, AI-2-dependent niche occupation by E. coli altered S. Tm metabolism at different stages of infection. Collectively, our findings highlight how AI-2 signaling in one species can affect the metabolism of its interaction partners in vivo .