多肽突变体Cbf-14-2抗青霉素耐药细菌的活性研究

发布时间：2018-04-09 01:22

本文选题：抗菌肽　切入点：Cbf--　出处：《中国药科大学学报》2017年04期

【摘要】：本研究主要探讨了新型多肽突变体Cbf-14-2对携带NDM-1基因重组菌(E.coli BL21(DE3)-NDM-1)的抗菌活性及机制。实验采用肉汤倍比稀释活菌计数法测定多肽对E.coli BL21(DE3)-NDM-1重组菌的MIC/MBC和杀菌曲线,评价多肽的体外抗菌活性;采用重组菌腹腔感染法建立小鼠败血症模型,评价多肽的体内抗菌活性;通过Zeta电位分析和流式细胞术探讨Cbf-14-2抗耐药细菌感染的作用机制。结果表明,多肽Cbf-14-2对携带NDM-1基因的耐药细菌具有良好的抗菌活性(MIC=16μg/m L),能在2 h内快速杀灭细菌;同时,多肽能显著降低感染小鼠肝、脾、肺和肾脏等组织的细菌负载量,对细菌显示出强效清除能力,将小鼠存活率由10%提高至70%。这主要由于Cbf-14-2能与细菌细胞膜表面负电荷发生静电结合,增加对膜的穿透能力。因此,Cbf-14-2有望成为治疗NDM-1耐药细菌诱发感染的潜在抗菌剂。
[Abstract]:In this study, the antimicrobial activity and mechanism of a new polypeptide mutant Cbf-14-2 against E. coli BL21DE3- NDM-1 was studied.The MIC/MBC and bactericidal curves of polypeptides against E.coli BL21(DE3)-NDM-1 recombinant bacteria were determined by broth doubling dilution method, and the in vitro antibacterial activity of polypeptides was evaluated, and the septicemia model of mice was established by the method of intraperitoneal infection of recombinant bacteria to evaluate the antibacterial activity of polypeptides in vivo.Zeta potential analysis and flow cytometry were used to investigate the mechanism of Cbf-14-2 in resistance to bacterial infection.The results showed that polypeptide Cbf-14-2 had good antibacterial activity against drug-resistant bacteria carrying NDM-1 gene, and could kill bacteria quickly within 2 hours, and the amount of bacterial load in liver, spleen, lung and kidney of infected mice was significantly decreased.It showed strong scavenging ability to bacteria and increased the survival rate of mice from 10% to 70%.This is mainly due to the electrostatic binding of Cbf-14-2 to the negative charge on the surface of the bacterial cell membrane, which increases the penetration ability of the membrane.Therefore, Cbf-14-2 is expected to be a potential antimicrobial agent for the treatment of NDM-1-resistant bacteria-induced infections.
【作者单位】：中国药科大学微生物学教研室;
【基金】：国家自然科学基金资助项目(No.81673483) 中央高校基本科研业务费专项资金资助(No.2632017PT03) 江苏高校优势学科建设工程资助项目(PADA)~~
【分类号】：R96

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