舒巴坦对鲍曼不动杆菌突变选择窗与外膜蛋白相关性研究

Study of Sulbactam against relationship between Acinetobacter baumannii selection window and outer membrane protein

目的探索鲍曼不动杆菌耐药机制,完善防耐药突变浓度(MPC)理论,指导临床合理用药。方法通过测定临床分离鲍曼不动杆菌的MPC相关参数,研究舒巴坦的防耐药突变能力,并对突变浓度诱导菌株进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE),探索外膜蛋白(OMP)表达量与耐药之间关系。结果舒巴坦对临床分离5株鲍曼不动杆菌耐药选择指数分别为6.4、7.2、5.6、9.9、5.6,诱导后的菌株OMP 29 k D条带减弱,提示鲍曼不动杆菌在突变浓度的舒巴坦诱导下,碳青霉烯耐药相关性外膜蛋白(Car O)低表达。结论舒巴坦对鲍曼不动杆菌耐药突变选择窗(MSW)的形成与Car O低表达可能密切相关,OMP的缺失可能是鲍曼不动杆菌耐药的首要机制;舒巴坦药代动力学参数表明,在临床应用中应避免其单独使用,联合用药可以减小或者关闭MSW,并减慢耐药菌株的产生速度。

Objective To explore Acinetobacter baumannii resistance mechanisms and improve mutant prevention concentration（MPC） theory for guiding clinical therapy. Methods The mutant prevention ability of Sulbactam was investigated by measuring relevant parameter of MPC of the clinically isolated Acinetobacter baumannii. SDS-polyacrylamide gel electrophoresis（SDS-PAGE） was performed to explore the relationship between outer membrane protein expression of mutant concentration induced strain and drug resistance. Results The resistance selection index of Sulbactam against five clinically isolated Acinetobacter baumannii was 6.4,7.2,5.6,9.9 and 5.6 respectively. The membrane protein band at 29 k D was weaken after the mutant induction,which indicated that the expression of Carbapenem associated resistance outer membrane protein（Car O） of Acinetobacter baumannii induced by Sulbactam at mutation concentration was low. Conclusion The mutant selection window（MSW） formation of Acinetobacter baumannii caused by Sulbactam may be closely related to low expression of Car O. The primary mechanism of drug resistance in Acinetobacter baumannii maybe owing to its membrane protein deficiency. The pharmacokinetic parameters of Sulbactam indicate that single medication should be avoided in clinical application. Combination drug therapy can reduce or close MSW and slow down the speed of drug-resistant strains generation in treatment of Acinetobacter baumannii infection.