The LuxS/AI-2 Quorum Sensing System-mediated Interspecies Interactions Of The Prokaryotes

Quorum Sensing(QS)is a ubiquitous cell-to-cell signaling mechanism in that cells regulate the expression of genes in response to changes in the concentration of AIs in the environment,thereby improving microbial population function and enhancing their ability to survive in complex environments.AI-2 serves one of the important AIs and mediates intraspecific and interspecific communication in prokaryotes.At present,most of the studies mainly focus on the regulation of physiological function and the treatment strategy against pathogenic bacteria in monospecies culture microorganism mediated by LuxS/AI-2 QS system.However,few reports on the biological function of the LuxS/AI-2 QS system in microhabitats were performed.Hence,this study takes the prokaryotic genomes of different sources(earth’s microbiomes,rumen,ocean,soil,rhizosphere,mouse gastrointestinal tract,and non-redundant prokaryotic databases)as the research object,and explores the role of the LuxS/AI-2 QS system in different microhabitats,and the expression level of these proteins in real habitat was further verified within the meta-transcriptomic data.Eventually,the pathogenic mechanism of Yersinia pseudotuberculosis mediated by the LuxS/AI-2 QS system was further studied,and the results are as follows:1.The LuxS/AI-2 QS system mediates rumen microbial interspecific communicationBy integrating the rumen culturable microbial genomes and the non-culturable microbial assembly genomes,the genes related to 8/15 types of signaling molecules were identified in the rumen ecosystem,among which AI-2-related genes(including AI-2synthase and multiple types of receptors)were highly abundant and widely distributed,and nearly 70% of the microbial genome contained AI-2-related genes.In addition,we constructed a microbial communication network mediated by LuxS/AI-2 QS system,in which AI-2 signaling molecules are produced by luxS-containing bacteria and then sensed by AI-2 receptor-containing bacteria to activate corresponding genes(MCPs,HKs,SPs,GCPs,STKs,etc.),which participate in different signaling pathways to regulate the function of the microbial community.These results provide a deeper understanding of how bacteria induce AI-2-mediated interaction and coordinate their group behaviors.2.The LuxS/AI-2 QS system mediates interspecific communication of microbes in large-scale microhabitatsThe spatial distribution of AI-2 synthetase and multiple types of receptors in different habitats was determined by analyzing AI-2 synthetase and multiple types of receptors in52515 MAGs assembled from 10,450 metagenomic samples worldwide.Further,we compared the AI-2 synthase,receptor types and delivery patterns of AI-2 in the prokaryotic genomes from ocean,soil,rhizosphere,and mouse gastrointestinal tract,and found that AI-2-mediated microbial communication was ubiquitous,but the receptor-mediated communication patterns were different in different habitats,among which CahR-type AI-2receptors were most abundant,followed by Lsr B.Further studies suggest the AI-2-based QS systems may play an important role by regulating the QS function of important microbial groups in different habitats.3.LuxS/AI-2 quorum sensing systems are widely present in prokaryotesThrough the analysis of non-redundant prokaryotic genomes,it was found that AI-2synthetases and receptors are widely present in prokaryotes and their delivery modes are diverse.The wide distribution and predictive function of the CahR and Lsr B receptors in prokaryotes were further studied,which greatly expands the current understanding of the distribution range and function of the CahR and Lsr B receptors.4.AI-2 mediates the physiological functions and pathogenicity of Yersinia pseudotuberculosis via the CahR-type receptor YcrAIn order to study the pathogenic mechanism of Y.pseudotuberculosis mediated by the LuxS/AI-2 QS system,it was found that AI-2 can affect the chemotaxis,self-aggregation and biofilm formation of Y.pseudobinding through CahR-type receptor YcrA.In addition,we found that AI-2 enhanced the colonization of Y.pseudotuberculosis in mice via YcrA to enhance its pathogenicity,which provided new ideas for the treatment strategy of Yersinia members mediated by the QS system.In conclusion,this study found that AI-2 can mediate the microbial communication in the rumen and in natural microhabitats around the world and can mediate a series of social functions in prokaryotes.Further studies revealed that AI-2 induces the chemotaxis,selfaggregation,biofilm formation and pathogenicity of Y.pseudotuberculosis by regulating YcrA.This study expands the current understanding of the impact of the QS system on microbial function in microhabitats,and the regulation of pathogenicity of intestinal pathogenic bacteria by QS.