抗菌肽Protegrin1与抗生素对致病性大肠杆菌的体外联合药效

Interaction in Vitro between Antibacterial Peptide Protegrin-1 and Antibiotics to Pathogenic E.coli

为研究抗菌肽Protegrin-1(PG-1)的抑菌效果及其与抗生素之间的协同效应关系,应用基因工程方法表达PG-1;测定几种常用的抗菌药物(四环素、丁胺卡那霉素和多黏菌素B等)对致病性大肠杆菌的最小抑菌浓度(MIC),并分别检测其与PG-1联用后的抗菌效果,采用分级抑制浓度指数(FIC)来分析PG-1与抗生素之间的抗菌作用关系,并进一步检测联合应用对细菌裂解率的影响。结果显示,PG-1与多黏菌素B、丁胺卡那霉素及四环素联用对大肠杆菌有协同作用,且PG-1与多黏菌素B联用可以提高细菌裂解率。PG-1与一些抗生素存在协同或者相加作用,临床上使用PG-1可以在一定程度上减少甚至替代抗生素的使用。

To investigate the antibacterial activity of protgerin-1 and its synergic interaction with antibiotics,the Protegrin-1 was expressed in P.pastoris.Nine clinically used antibiotics,including tetracycline,amikacin sulfate,polymyxin B,cefradine,florfenicol,ciprofloxacin,norfloxacin,levofloxacin,streptomycin sulfate,were selected.In vitro antibacterial activities of the porcine antibacterial peptide Protegrin-1,alone or in combination with the antibiotics were measured by MIC.Synergy was surveyed when the antibacterial peptide was combined with the nine clinically used antibiotics by FIC.In the end,the bacterial lysis of Protegrin-1 was detected.The results showed that the antibacterial peptide had synergic interaction with amikacin,tetracycline and polymyxin B.The lysis rate of E.coli was increased substantially in the presence of the combination of Protegrin-1 and polymyxin B.The results demonstrated that the effect of combination was synergistic or enhancement.The antibacterial peptide can reduce the using of antibiotics,and further studies are needed to analyze the antibacterial mechanism and their relationship.