Autoinducer‐2 Quorum Sensing Is an Active Universal Signaling System in Sociomicrobiology

Autoinducer-2 (AI-2) is a bacterial quorum sensing (QS) signaling molecule that regulates inter-specific and intraspecific bacterial communication in complex ecological environments. Here, we systematically analyzed the distribution of AI-2 QS-related proteins (synthases and receptors) in the domain bacteria, explored the evolution and development of AI-2 receptors, and analyzed the AI-2 regulatory networks using human intestinal metagenomic data. The results show that AI-2 QS-related proteins are distributed in 17 bacterial phyla, accounting for approximately 36.80% of the total genomes. Based on the ability of bacteria to synthesize and receive AI-2 signals, we divided bacteria into four major categories, namely Prosumer, Producer, Monitor, and Immunizer. The Gram-positive bacteria are mainly responsible for producing the AI-2 signals, while Gram-negative bacteria are more likely to respond to AI-2. Evolutionary analysis shows that the AI-2 receptor CahR is mainly derived from the methyl-accepting chemotaxis protein (MCP). Based on the length difference of the ligand-binding domains, we further speculate that AI-2 binding activates CahR through either allostery or aggregation mode. Using human intestinal metagenomic data, we found a strong correlation between AI-2 signaling and c-di-GMP signaling. These findings will have an important impact on the AI-2 QS research and accelerate its development.