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作 者:杨晓倩 蒋美玲 史翔宇 黄亚 吴皓旻 马菱蔓 周长林[1] YANG Xiao-qian;JIANG Mei-ling;SHI Xiang-yu;HUANG Ya;WU Hao-min;MA Ling-man;ZHOU Chang-lin(School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China)
机构地区:[1]中国药科大学生命科学与技术学院,江苏南京210009
出 处:《药物生物技术》2018年第5期383-389,共7页Pharmaceutical Biotechnology
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);中国博士后科学基金第62批面上资助(No.1600010009)
摘 要:多肽Cbf-14是由14个氨基酸组成的抗菌肽,该课题研究了其对临床常见的G+和G-细菌的抑菌活性。通过琼脂平板稀释法和微量肉汤稀释法测定了多肽Cbf-14对临床常见菌株的最低抑菌浓度(MIC)和最低杀菌浓度(MBC);通过改变接种量,培养基pH,研究不同条件对多肽Cbf-14抑菌活性的影响。体外抗菌活性实验结果表明,多肽Cbf-14对多种临床常见敏感和耐药细菌均有良好的抑菌活性,对部分耐药菌株的MIC为16μg/m L,且能在4~8 h内快速杀灭细菌,同时pH稳定性好;通过耐受诱导试验研究多肽Cbf-14是否容易诱导细菌耐药。结果表明,不同细菌在亚抑菌浓度的Cbf-14中连续诱导10代后,MIC值基本保持不变,说明Cbf-14不容易诱导细菌耐药;研究结果提示其可以作为临床抗耐药细菌感染的候选药物。Antimicrobial peptide Cbf-14 is composed of 14 amino acids. In this study,the antibacterial activity of peptide Cbf-14 against commonly clinical G+and G-strains was detected. We determined the minimum inhibitory concentration(MIC) and minimum bactericidal concentration(MBC) of Cbf-14 against these test strains by agar plate dilution method and micro broth dilution method. According to the data of MIC,the disk diffusion antibacterial assay was performed to evaluate the bacteriostatic activity of Cbf-14. Furthermore we investigated the effects of inoculum concentration and medium pH change on the antibacterial activity of Cbf-14. Ultimately,the resistance studies were performed by exposing bacteria to sub-MIC Cbf-14 or antibiotics to study whether Cbf-14 could induce bacterial resistance easily. The results showed that Cbf-14 exerted potent antibacterial activity against multiple clinical isolates,with MICs against some resistant strains of 16 μg/m L. Importantly,the test strains could be killed within 4 ~ 8 h. In addition,the MICs of Cbf-14 was relatively stable,when the medium pH ranged from 3 ~ 8. Interestingly,a period of time after exposure to sub-MIC peptide or antibiotics,serial strains emerged resistance to antibiotics but not Cbf-14. In summary,this peptide can be used as a clinical candidate drug fortreatment of bacterial infection.
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