群体感应系统信号分子受体abaR基因对鲍曼不动杆菌致病性和获得性耐药的影响  

Effect of the quorum sensing system LuxR type regulator abaR on thepathogenicity and drug resistance of Acinetobacter baumannii

作　　者：廖佳馨 胡韦维 Liao Jiaxin;Hu Weiwei(Department of Respiratory and Critical Care,The First Affiliated Hospital of Chongqing Medical University)

机构地区：[1]重庆医科大学附属第一医院呼吸与危重症学科,重庆400016

出　　处：《重庆医科大学学报》2025年第1期52-57,共6页Journal of Chongqing Medical University

基　　金：重庆市自然科学基金面上资助项目(编号:cstc2020jcyjmsxmX0207)。

摘　　要：目的:探讨群体感应系统(quorum sensing system,QS)信号分子受体abaR对鲍曼不动杆菌致病性和耐药性的影响。方法:构建鲍曼不动杆菌ATCC 17978 abaR敲除株(ΔabaR),通过生长曲线分析、血清杀伤实验和生物膜形成实验,比较野生株和敲除株在生长速率、血清杀伤能力和生物膜形成能力等方面的差异;通过多步骤稳态体外诱导耐药实验,检测野生株ATCC 17978和敲除株ΔabaR诱导耐药后相关耐药基因表达水平的差异。结果:生长曲线显示,野生株和敲除株在各个时期的600 nm处测定吸光度(absorbance,A)值无明显差异(t=10.720,P>0.05);血清杀伤实验表明,敲除株的健康人血清(normal human serum,NHS)/磷酸缓冲盐溶液(phosphate buffered saline,PBS)比值明显低于野生株(t=3.968,P<0.05);生物膜形成实验显示,敲除株的生物膜形成能力在培养的前24 h低于野生株(t=4.632,P<0.01);在体外将野生株和敲除株诱导为美罗培南耐药菌株后,敲除株的耐药基因AdeA、AdeB和AmpC表达水平低于野生株(t_(1)=11.330;t_(2)=15.010;t_(3)=13.420,均P<0.001)。结论:abaR基因通过调控生物膜形成和外排泵基因的表达,明显影响鲍曼不动杆菌的毒力和获得性耐药;干扰群体感应系统中的abaR受体分子可能是抑制群体感应信号和解决鲍曼不动杆菌耐药性问题的有效策略,为开发新型抗生素治疗耐药菌株奠定了基础。Objective:To investigate the effect of the quorum sensing(QS)system LuxR type regulator abaR on the pathogenicity and drug resistance of Acinetobacter baumannii.Methods:The abaR-knockout(ΔabaR)strain of A.baumannii ATCC 17978 was constructed,and the growth curve analysis,serum killing experiment,and biofilm formation assay were used to compare the wild strain and theΔabaR strain in terms of growth rate and serum killing ability.The multi-step in vitro drug resistance induction test was used to investigate the differences in the expression levels of related drug resistance genes after induction of drug resistance between the ATCC 17978 wild strain and theΔabaR strain.Results:The growth curve showed that there was no significant difference in A600 nm value between the wild strain and theΔabaR strain at each time point(t=10.720,P>0.05).The serum killing experiment showed that theΔabaR strain had a significantly lower normal human serum/phosphate buffered saline(NHS/PBS)ratio than the wild strain(t=3.968,P<0.05).The biofilm formation assay showed that theΔabaR strain had a significantly lower biofilm formation ability than the wild strain within the first 24 hours of culture(t=4.632,P<0.01).After the wild strain and theΔabaR strain were induced to meropenem-resistant strains in vitro,compared with the wild strain,theΔabaR strain had significantly lower expression levels of the drug-resistance genes AdeA,AdeB,and AmpC(t_(1)=11.330;t_(2)=15.010;t_(3)=13.420,P<0.001).Conclusion:The abaR gene significantly influences the virulence and acquired resistance of A.baumannii by regulating biofilm formation and the expression of efflux pump genes.Interference with the abaR receptor molecule within the QS may be an effective strategy to inhibit QS signaling and address the drug resistance of A.bau⁃mannii,which lays a foundation for developing novel antibiotics for the treatment of drug-resistant strains.

关 键 词：鲍曼不动杆菌 abaR基因 毒力 生物被膜 获得性耐药 

分 类 号：R378.99[医药卫生—病原生物学]