Using Pangenome To Effectively Screen Genes Related To Bacterial Molecular Function

The spreads of pathogen have caused huge burden in the healthy and economics worldwide,which is a serious public health problem that needs to be attention and solved.Among them,Acinetobacter baumannii,Clostridium difficile and Enterococcus faecalis are three frequently observed pathogens,which can cause nosocomial infection through medical equipment or fecal-oral route,causing infection of respiratory tract,intestinal tract,urinary tract and even central nervous system,seriously threatening the health of patients and medical staff.In the recent years,most of research on bacteria focused on their emerged antimicrobial resistance,enhanced virulence and the horizontal transfer of the drug resistance genes.With the development of sequencing technology,the cost of deep sequencing were decreased rapidly,which makes the genome sequencing much easier and generate amount of bacterial genomes(both draft genome and complete genome).In addition,the understanding of the bacterial have shift from a single bacteria to understand the bacteria in a ecology.Therefore,the understanding of the bacterial genome also changed from one genome to pan-genome or metagenome.Pan-genome analysis is a new bacterial research paradigm,which provided more comprehensive and systematic genome information of a bacterial population,and benefit improve the understanding the evolutionary process of bacterial drug resistance,enhanced virulence and predict the evolutionary divergence process.In this study,we firstly constructed a pan-genome analysis pipeline,and performed the bioinformatics analysis on the Acinetobacter baumannii,Clostridium difficile and Enterococcus faecalis.Sequencing data of clinical strains and genomic data in the public database were used in our analysis.Applying this new bioinformatics pipeline into three major clinical strains,ⅰ)we observed new clade of Acinetobacter baumannii(Clade 4),which widely spread in our hospital for a long-term.In addition,an OprD protein was identified specifically in the clade,and further confirmed as the virulence gene.ⅱ)The pan-genome analysis on Clostridium difficile suggested that high virulent strain Clostridium difficile A-B+spread rapidly from 2011 to 2019,which emerged as a new molecular typing types ST360 and ST361.iii)We found that significant differences in gene composition between blood-derived Enterococcus faecalis and gastrointestin-derived Enterococcus faecalis,especially in fsr quorum sensing system.Among them,the proportion of genes in blood-derived strains was higher,whilst that is low in gastrointestinal tract.Meanwhile,the gene island pattern was different,Cluster I in blood and Cluster III in gastrointestinal tract.In conclusion,we conducted massive studies on the pangenomic characteristics of common clinical infectious bacteria by the locally constructed bacterial pangenome analysis pipeline,which could provide more information for better understanding of the microbe and improvement of clinical treatment strategies.