中国现代中药2025，Vol.27Issue(5)：804-812,9.DOI:10.13313/j.issn.1673-4890.20241202003
6株耐碳青霉烯铜绿假单胞菌的全基因组序列分析及痰热清注射液对其抑菌作用考察
Whole-Genome Sequence Analysis of Six Strains of Carbapenem-Resistant Pseudomonas aeruginosa and Antibacterial Effect of Tanreqing Injection
摘要
Abstract
Objective:This paper aims to understand the basic whole genome characteristics of carbapenem-resistant Pseudomonas aeruginosa(CRPA)with different drug resistance phenotypes and investigate the antibacterial effect of Tanreqing Injection(TRQ),so as to analyze the relationship between genomic polymorphism of CRPA and clinical efficacy.Methods:Six strains of CRPA with different drug resistance phenotypes were selected,and their multi-locus sequence typing(MLST)and accessory genomes were analyzed by Illumina high-throughput sequencing.The efficacy of TRQ alone and combined with imipenem(IPM)was evaluated on the above six CRPA strains,and the genome-related pathogenic system of each strain was further analyzed;core and specific genes were compared,and the metabolic pathways related to β-lactam resistance were analyzed.Results:The genome of the six strains ranged from 6.5 to 6.9 Mbp,with great differences in size,belonging to five sequence types(ST),and three strains belonged to high-risk clonotype ST111(PA68 and PA94)and ST235(PA115).There were significant differences in the types,quantities,and distribution of each strain's accessory genomes.TRQ only showed an antibacterial effect on high-risk clonotypes PA68 and PA115 and exerted a synergetic or partially synergetic effect with IPM on non-high-risk clonotypes.There was no significant difference between the drug resistance and virulence genes of the six CRPA strains.The drug resistance genes were mainly related to increasing antibiotic effluence,producing passivating enzymes,and modifying the main binding targets of antibiotics.The virulence genes were mostly offensive virulence factors,mainly related to adhesion,secretion,and iron uptake.Each strain contained unique genes,mostly related to the secretion system,multidrug transporter,and multidrug efflux genes.By analyzing the metabolic pathways related to β-lactam resistance,the drug resistance of six CRPA strains was mainly related to the reduction of outer membrane porin,efflux pump,the production of hydrolase,etc.Conclusion:CRPA carries a large number of drug resistance genes and virulence genes,and the TRQ-IPM combination shows a preferable synergistic antibacterial effect against non-high-risk CRPA clonotypes;MLST and drug resistance phenotype of strains may be one of the reasons for the clinical efficacy difference of TRQ,which provides references for subsequent studies on molecular epidemiology,clinical drug use,and pathogenicity mechanism.关键词
耐碳青霉烯铜绿假单胞菌/全基因组测序/痰热清注射液/耐药基因/毒力基因Key words
carbapenem-resistant Pseudomonas aeruginosa/whole-genome sequencing/Tanreqing Injection/drug resistance gene/virulence gene分类
预防医学引用本文复制引用
吴娅丽,唐进法,秦玺,汪彬,李伟霞,王晓艳,陈小菲,张明亮,张辉,杨柳青..6株耐碳青霉烯铜绿假单胞菌的全基因组序列分析及痰热清注射液对其抑菌作用考察[J].中国现代中药,2025,27(5):804-812,9.基金项目
河南省科技研发计划联合基金项目(232301420083) （232301420083）
河南省中医药科学研究专项(2023ZXZX1026) （2023ZXZX1026）
河南省高等学校重点科研项目(23A360008) （23A360008）
河南省高校科技创新团队项目(23IRTSTHN026) （23IRTSTHN026）
