铜绿假单胞菌生物被膜基因表达生物信息学研究  

Bioinformatics analysis of Pseudomonas aeruginosa biofilm on gene expression

作　　者：廖黎[1] 鲁兰[1] 杨晨[1] 刘昆[1] 赵玉婷 Liao Li;Lu Lan;Yang Chen;Liu Kun;Zhao Yu-Ting(Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of Pharmacy,Chengdu University,Chengdu 610106)

机构地区：[1]抗生素研究与再评价四川省重点实验室,四川抗菌素工业研究所,药学院,成都大学,成都610106

出　　处：《中国抗生素杂志》2022年第10期1084-1090,共7页Chinese Journal of Antibiotics

基　　金：国家自然科学基金(No.81803812)。

摘　　要：目的通过生物信息学探究铜绿假单胞菌生物被膜形成的差异表达基因及可能作用机制。方法通过GEO数据库筛选获得铜绿假单胞菌生物被膜数据芯片GSE120760,GEO2R工具筛选出铜绿假单胞菌浮游状态和生物被膜状态的差异表达基因;差异表达基因通过String数据库和Cytoscape3.7.1软件中构建靶点PPI网络图,并在DAVID和KOBAS数据库中对差异表达基因进行GO生物富集和KEGG通路分析。用铜绿假单胞菌体外生物被膜模型测定5种氨基酸(D/L型)的抗生物被膜作用效果。结果由芯片GSE120760筛选得到556个差异表达基因,其中上调基因143个,下调基因413个;从差异表达基因中筛选到62个关键基因,这些基因主要与30S和50S核糖体蛋白相关;GO功能富集得到40个条目;KEGG富集到44条通路,主要涉及代谢途径、次生代谢产物的生物合成、氨基酸生物合成通路、多种氨基酸代谢、群体感应、氨酰tRNA生物合成通路等;体外验证试验中,D-氨基酸对铜绿假单胞菌生物被膜有抑制作用,而L-氨基酸对其形成无影响。结论通过生物信息学挖掘出铜绿假单胞菌生物被膜形成的关键基因与靶点,并与代谢途径、氨基酸合成和代谢、群体感应、氨酰tRNA生物合成通路等相关,为铜绿假单胞菌生物被膜的靶向抗感染药物的研发提供思路。Objective The aim of study is to investigate differentially expressed genes(DEGs)in the biofilm formation of Pseudomonas aeruginosa(PA)and its possible mechanism through bioinformatics analysis.Methods Data chip GSE120760 of biofilm in Pseudomonas aeruginosa was obtained in GEO database.The DEGs in planktonic status and biofilm status of PA were identified by GEO2R.The PPI network map of DEGs was constructed by string database and Cytoscape 3.7.1 software.In David and Kobas database,GO bioaccumulation and KEGG pathway analysis were carried out on DEGs.The anti-biofilm effects of five amino acids(D/L)were determined by the in vitro biofilm model of PA.Results Five hundred and fifty-six DEGs were selected from GSE120760,including 143 up-regulated genes and 413 down-regulated genes.Sixty-two key genes were screened out from DEGs,which were mainly related to 30S and 50S ribosomal proteins.Forty items were enriched in GO function.In KEGG pathway analysis,forty-four pathways were obtained,which were mainly related to metabolic pathway,biosynthesis of secondary metabolites,biosynthesis of amino acid,amino acid metabolism,quorum sensing,aminoacyl-tRNA biosynthesis.In vitro,D-amino acids had inhibitory effects on PA biofilm formation,while L-amino acids had no effect on PA biofilm formation.Conclusion Key genes in PA biofilm formation were identified by bioinformatics analysis,which was related to metabolic pathway,biosynthesis and metabolism of amino acid,aminoacyl-tRNA biosynthesis.Our findings would provide ideas for the development of anti-infective drugs targeting biofilm in PA.

关 键 词：铜绿假单胞菌 生物被膜 生物信息学 差异表达基因 D-氨基酸 L-氨基酸 

分 类 号：R9[医药卫生—药学]