比较基因组学分析弧菌属群体感应通路的分布与进化

Comparative genomic analysis of the distribution and evolution of quorum sensing pathways in the Vibrio genus

群体感应是一种细菌细胞间的通讯过程,细菌通过测量细胞外自诱导剂浓度从而感知群体细胞密度变化。群体感应使细菌能够在两种基因表达模式下转换:在低细胞密度时有利于个体发展,而在高细胞密度时则有利于群体发展。目前主要有7种群体感应通路,分别以oligopeptides、AHL(Acylated Homoserine Lactones)、AI-2(Autoinducer-2)、CAI-1(Cholera Autoinducer-1)、PQS(Pseudomonas Quinolone Signal)、AI-3(Autoinducer-3)以及DSF(Diffusible Signal Factor)作为各群体感应通路的信号分子;其中oligopeptides存在于革兰氏阳性细菌中,其余6种信号分子存在于革兰氏阴性细菌中。弧菌是导致人类感染和水产品污染的主要病原菌,传统的抗生素治疗弧菌感染具有很强的选择压力,导致越来越多耐药弧菌出现。面对愈发严峻的弧菌耐药性问题,目前群体感应淬灭被认为是治疗弧菌感染的重要替代手段之一,因而有必要调查弧菌属细菌不同群体感应通路的分布情况,为针对弧菌的群体感应淬灭剂研发提供重要参考信息。通过比较基因组学分析,发现全基因组测序的46株弧菌存在AHL、AI-2以及CAI-1这3种信号分子通路,其中5株弧菌均含有上述3种信号分子通路,共有30株弧菌只含有AI-2和CAI-1两种信号分子通路;而46株弧菌都不存在PQS、AI-3以及DSF群体感应通路。此外,弧菌群体感应通路的分布与物种进化有关,含有同种群体感应信号分子通路的弧菌,其亲缘关系较近,说明该通路的基因进化自它们的共同祖先。本研究表明开发针对弧菌的群体感应淬灭剂应以AI-2和CAI-1两种信号分子介导的通路作为靶点。

Quorum sensing(QS)is a process of bacterial cell-cell communication in which bacteria can monitor their population density by detection of extracellular autoinducer.QS allows the bacteria to switch between two kinds of gene expression modes:The program is suitable for individual development at low cell density,while favoring community at high cell density.Presently,there are mainly seven kinds of QS signaling molecules,including oligopeptides,AHL(Acylated Homoserine Lactones),AI-2(Autoinducer-2),CAI-1(Cholera Autoinducer-1),PQS(Pseudomonas Quinolone Signal),AI-3(Autoinducer-3),and DSF(Diffusible Signal Factor).Among them,oligopeptides mainly exist in gram-positive bacteria,and the others are commonly found in gram-negative bacteria.Species of the Vibrio genus are important pathogens for human and aquaculture.Since traditional antibiotic treatment has a strong selection pressure leading to increasing number of drug-resistant Vibrio and increasing serious problems,QS quenching is believed as one alternative strategy of the most potential to combat bacterial infection.Thus,it is necessary to investigate the distribution of QS pathways among the Vibrio genus.Among the 46 whole genome sequenced Vibrio species,we found that only three pathways exist in Vibrio species,including AHL,AI-2 and CAI-1 pathways.Specifically,five Vibrio species contain the above three pathways,and 30 strains contain both AI-2 and CAI-1 pathways.However,none of the 46 Vibrio species have the PQS,AI-3 and DSF pathways.In addition,the distribution of QS pathways in Vibrio is related to their phylogeny,suggesting that species with the same QS pathway(s)are close relatives,which indicates that the genes of this pathway evolved from their common ancestor.This study provides useful information for QS quenching against Vibrio pathogens by targeting the AI-2 and CAI-1 QS pathways.