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

ABSTRACT 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.