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一种在ML35中具有两个抗菌作用靶点的新型合成肽。

A New Synthetic Peptide Having Two Target of Antibacterial Action in ML35.

作者信息

Barreto-Santamaría Adriana, Curtidor Hernando, Arévalo-Pinzón Gabriela, Herrera Chonny, Suárez Diana, Pérez Walter H, Patarroyo Manuel E

机构信息

Receptor-Ligand Department, Fundación Instituto de Inmunología de ColombiaBogotá, Colombia; Faculty of Sciences and Education, Universidad Distrital Francisco José de CaldasBogotá, Colombia; School of Medicine and Health sciences, Universidad del RosarioBogotá, Colombia.

Receptor-Ligand Department, Fundación Instituto de Inmunología de ColombiaBogotá, Colombia; School of Medicine and Health sciences, Universidad del RosarioBogotá, Colombia.

出版信息

Front Microbiol. 2016 Dec 20;7:2006. doi: 10.3389/fmicb.2016.02006. eCollection 2016.

Abstract

The increased resistance of microorganisms to the different antimicrobials available to today has highlighted the need to find new therapeutic agents, including natural and/or synthetic antimicrobial peptides (AMPs). This study has evaluated the antimicrobial activity of synthetic peptide 35409 (RYRRKKKMKKALQYIKLLKE) against ATCC 29213, ATCC 15442 and ML 35 (ATCC 43827). The results have shown that peptide 35409 inhibited the growth of these three bacterial strains, having 16-fold greater activity against and , but requiring less concentration regarding (22 μM). When analyzing this activity against compared to time taken, it was found that this peptide inhibited bacterial growth during the first 60 min and reduced CFU/mL 1 log after 120 min had elapsed. This AMP permeabilized the membrane by interaction with membrane phospholipids, mainly phosphatidylethanolamine, inhibited cell division and induced filamentation, suggesting two different targets of action within a bacterial cell. Cytotoxicity studies revealed that peptide 35409 had low hemolytic activity and was not cytotoxic for two human cell lines. We would thus propose, in the light of these findings, that the peptide 35409 sequence should provide a promising template for designing broad-spectrum AMPs.

摘要

如今,微生物对现有不同抗菌药物的耐药性增强,凸显了寻找新治疗药物的必要性,其中包括天然和/或合成抗菌肽(AMPs)。本研究评估了合成肽35409(RYRRKKKMKKALQYIKLLKE)对ATCC 29213、ATCC 15442和ML 35(ATCC 43827)的抗菌活性。结果表明,肽35409抑制了这三种细菌菌株的生长,对[具体菌株1]和[具体菌株2]的活性高16倍,但对[具体菌株3]所需浓度较低(22 μM)。在分析其对[具体菌株3]的活性与作用时间的关系时发现,该肽在最初60分钟内抑制细菌生长,120分钟后使CFU/mL降低1个对数。这种抗菌肽通过与膜磷脂(主要是磷脂酰乙醇胺)相互作用使[具体菌株3]的细胞膜通透性增加,抑制细胞分裂并诱导丝状体形成,表明在细菌细胞内有两个不同的作用靶点。细胞毒性研究表明,肽35409具有低溶血活性,对两种人类细胞系无细胞毒性。因此,根据这些发现,我们认为肽35409序列应为设计广谱抗菌肽提供一个有前景的模板。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b71e/5167725/5f86183a521e/fmicb-07-02006-g001.jpg

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