亚抑菌浓度亚胺培南通过影响Ⅳ型菌毛增强耐药鲍曼不动杆菌的生物膜形成  

Sub-minimal inhibitory concentration of imipenem enhances biofilm formation of resistant Acinetobacter baumannii isolates by affecting type Ⅳ pili

作　　者：樊莉 李聃丹 田竞[2] 孙凤军 冯伟 周世文 FAN Li;LI Dandan;TIAN Jing;SUN Fengjun;FENG Wei;ZHOU Shiwen(Department of Pharmacy,Second Affiliated Hospital,Army Medical University（Third Military Medical University）,Chongqing,400037;Department Teaching Support,3 Department of Pharmacy,First Affiliated Hospital,Army Medical University（Third Military Medical University）,Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学)第二附属医院药学部,重庆400037 [2]陆军军医大学(第三军医大学)教学保障处,重庆400038 [3]陆军军医大学(第三军医大学)第一附属医院药学部,重庆400038

出　　处：《第三军医大学学报》2018年第21期1967-1972,共6页Journal of Third Military Medical University

摘　　要：目的探讨在亚抑菌浓度(sub-minimal inhibitory concentration,sub-MIC)亚胺培南(imipenem,IMP)的作用下,IMP耐药和敏感鲍曼不动杆菌生物膜形成能力的变化。方法采用琼脂平板倍比稀释法检测IMP耐药和敏感鲍曼不动杆菌的最低抑菌浓度(minimal inhibitory concentration,MIC);采用PCR扩增鉴定碳青霉烯酶耐药基因;在给予sub-MIC IMP干预后,以微孔法检测细菌生物膜的形成,菌落平板计数法检测细菌粘附能力的改变,泳动实验观察细菌的运动性,定量RT-PCR检测细菌Ⅳ型菌毛基因的表达。结果 10株IMP耐药鲍曼不动杆菌基因扩增结果显示所有菌株含有OXA-51基因,9株含有OXA-23基因,只有3株携带IMP-4基因。sub-MIC IMP对IMP耐药鲍曼不动杆菌的生物膜形成、粘附性和运动性均有显著的诱导作用,而对IMP敏感菌株的生物膜形成、粘附性和运动性未发现一致性的作用(5株抑制,3株无作用,2株诱导)。sub-MIC IMP诱导鲍曼不动杆菌生物膜形成的菌株中均出现了Ⅳ型菌毛基因表达的增加。结论 sub-MIC IMP可能通过影响Ⅳ型菌毛介导的粘附运动能力,使耐药菌株的生物膜形成显著增强。Objective To investigate the changes in the biofilm formation of imipenem-resistant and sensitive Acinetobacter baumannii（ A. baumannii） isolates under the sub-minimal inhibitory concentration of imipenem（ sub-MIC IMP）. Methods MIC values were detected by agar plate dilution in both imipenemresistant and sensitive A. baumannii isolates. The carbapenemase resistance genes were amplified by PCR.After the intervention of sub-MIC IMP,the biofilm formation was detected by micro-well method,the bacterial adhesion was detected by colony plate counting,and the bacterial motility was observed by swimming,and the expression of the bacterial type IV pili gene was detected by quantitative RT-PCR. Results The results of carbapenemase resistance genes showed there were 10 strains of IMP-resistant A. baumannii carrying OXA-51 gene,9 carrying OXA-23 gene and only 3 IMP-4 gene. Sub-MIC IMP significantly induced the biofilm formation,adhesion and motility of IMP-resistant A. baumannii,but no such changes were found in above aspects in the IMP-sensitive strains（ 5 strains exhibited inhibitory effects,3 showed no effect,and 2 presented induction）. Enhanced expression level of type Ⅳ pili gene was found in all the strains with sub-MIC IMP induced biofilm formation. Conclusion Sub-MIC IMP may significantly enhance the biofilm formation of A.baumannii by affecting the Ⅳ pili related adherence and motility.

关 键 词：亚抑菌浓度 亚胺培南 鲍曼不动杆菌 生物膜 耐药性 

分 类 号：R378.7[医药卫生—病原生物学] R915[医药卫生—基础医学]