Autoinducer-2 signaling promotes intestinal colonization of Aeromonas veronii and induces cell apoptosis in loach (Misgurnus anguillicaudatus).

Abstract

Quorum sensing systems, particularly autoinducer-2 (AI-2) signaling, have significant effects on bacterial colonization and virulence. However, how they affect intestinal colonization by pathogens and subsequent host immune responses remains unclear. Here, we investigated the influence of AI-2 signaling on the intestinal colonization ability of Aeromonas veronii Z12 and the host's immune response. We found that AI-2 signaling promoted the colonization of A. veronii to the intestine of loach (Misgurnus anguillicaudatus) and caused severe intestinal damage, while D-ribose, an AI-2 signaling inhibitor, effectively inhibited the colonization of A. veronii. Transcriptomic sequencing elucidated the molecular mechanism of this damage, revealing upregulation of p53 pathway genes associated with apoptosis. Furthermore, intestinal microbiota dysbiosis induced by A. veronii colonization was associated with host cell apoptosis, leading to nitrite accumulation, which increased intracellular reactive oxygen species (ROS) levels, which activated the p53 pathway, and induction of cell apoptosis. These findings provide insights into the interaction among bacterial quorum sensing, intestinal microbiota, and the host immune response, which highlight potential therapeutic targets for mitigating bacterial-induced intestinal damage.IMPORTANCEThe intestinal colonization of pathogens regulated by autoinducer-2 (AI-2) signaling and its induced host response have not been fully characterized. Here, we revealed the effect of AI-2 on intestinal colonization of Aeromonas veronii and its induced cell apoptosis in loach. Our study demonstrated that the deficiency of AI-2 significantly reduced A. veronii colonization in the loach intestine and mitigated the tissue damage. Additionally, A. veronii colonization induced significant upregulation of p53 pathway genes and proteins, indicating a key role of AI-2 signaling in host responses. Understanding these mechanisms not only helps to elucidate the pathogenicity of A. veronii but also may provide broader insights into the pathogenic mechanisms of other pathogens, thus revealing general principles of pathogen-host interactions across different models. Furthermore, we found that A. veronii colonization led to intestinal microbiota dysbiosis, notably an increase in the abundance of Hypomicrobium sp., which was associated with nitrite accumulation, elevating reactive oxygen species levels, activating the p53 pathway, and inducing cell apoptosis. These findings provide important insights into the complex mechanisms of AI-2 signaling in bacterial-host interactions. Additionally, the regulatory role of AI-2 signaling may have potential clinical applications as an intervention strategy, offering new directions for developing treatments against intestinal infections.