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一种源自地中海海参的抗菌肽 Holothuroidin 2 的合成衍生物()在 控制中的应用。

A Synthetic Derivative of Antimicrobial Peptide Holothuroidin 2 from Mediterranean Sea Cucumber () in the Control of .

机构信息

Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche, Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy.

CNR-IOM-Democritos c/o International School for Advanced Studies (SISSA), Via Bonomea 265, 34136 Trieste, Italy.

出版信息

Mar Drugs. 2019 Mar 8;17(3):159. doi: 10.3390/md17030159.

Abstract

Due to the limited number of available antibiotics, antimicrobial peptides (AMPs) are considered antimicrobial candidates to fight difficult-to-treat infections such as those associated with biofilms. Marine environments are precious sources of AMPs, as shown by the recent discovery of antibiofilm properties of Holothuroidin 2 (H2), an AMP produced by the Mediterranean sea cucumber In this study, we considered the properties of a new H2 derivative, named H2d, and we tested it against seven strains of the dangerous foodborne pathogen . This peptide was more active than H2 in inhibiting the growth of planktonic and was able to interfere with biofilm formation at sub-minimum inhibitory concentrations (MICs). Atomic-level molecular dynamics (MD) simulations revealed insights related to the enhanced inhibitory activity of H2d, showing that the peptide is characterized by a more defined tertiary structure with respect to its ancestor. This allows the peptide to better exhibit an amphipathic character, which is an essential requirement for the interaction with cell membranes, similarly to other AMPs. Altogether, these results support the potential use of our synthetic peptide, H2d, as a template for the development of novel AMP-based drugs able to fight foodborne that are resistant to conventional antibiotics.

摘要

由于可用抗生素数量有限,抗菌肽 (AMPs) 被认为是对抗难以治疗的感染(如与生物膜相关的感染)的抗菌候选物。海洋环境是 AMPs 的宝贵来源,最近发现的来自地中海海参的 Holothuroidin 2 (H2) 的抗生物膜特性就是证明。在这项研究中,我们研究了一种名为 H2d 的新型 H2 衍生物的特性,并对其进行了七种危险食源性病原体 的测试。与 H2 相比,这种肽在抑制浮游生物生长方面更具活性,并且能够在亚最小抑制浓度 (MIC) 下干扰生物膜形成。原子级分子动力学 (MD) 模拟揭示了与 H2d 增强抑制活性相关的见解,表明与前身相比,该肽具有更明确的三级结构。这使得该肽能够更好地表现出两亲性,这是与细胞膜相互作用的必要条件,类似于其他 AMPs。总的来说,这些结果支持我们的合成肽 H2d 可作为开发新型基于 AMP 的药物的模板,用于对抗对传统抗生素具有耐药性的食源性病原体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0d6/6471310/19cc95470fbc/marinedrugs-17-00159-g001.jpg

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