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从海洋软体动物 （Gmelin，1791）中鉴定和表征三种新的抗菌肽。

Identification and Characterization of Three New Antimicrobial Peptides from the Marine Mollusk (Gmelin, 1791).

机构信息

Core Facility for Functional Peptidomics (CFP), Faculty of Medicine, Ulm University, 89081 Ulm, Germany.

Core Unit of Mass Spectrometry and Proteomics, Faculty of Medicine, Ulm University, 89081 Ulm, Germany.

出版信息

Int J Mol Sci. 2023 Feb 14;24(4):3852. doi: 10.3390/ijms24043852.

DOI:10.3390/ijms24043852
PMID:36835264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9968088/
Abstract

Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk . A pool of peptides was analyzed with nanoLC-ESI-MS-MS technology, and three potential antimicrobial peptides (Nv-p1, Nv-p2 and Nv-p3) were identified with bioinformatical predictions and selected for chemical synthesis and evaluation of their biological activity. Database searches showed that two of them show partial identity to histone H4 peptide fragments from other invertebrate species. Structural predictions revealed that they all adopt a random coil structure even when placed near a lipid bilayer patch. Nv-p1, Nv-p2 and Nv-p3 exhibited activity against . The most active peptide was Nv-p3 with an inhibitory activity starting at 1.5 µg/mL in the radial diffusion assays. The peptides were ineffective against , and . On the other hand, these peptides demonstrated effective antibiofilm action against , and but not against the planktonic cells. None of the peptides had significant toxicity on primary human macrophages and fetal lung fibroblasts at effective antimicrobial concentrations. Our results indicate that -derived peptides represent new AMP sequences and have the potential to be optimized and developed into antibiotic alternatives against bacterial and fungal infections.

摘要

贝类因其体液防御机制主要基于这些小分子而被广泛研究用于抗菌肽。在本报告中，我们描述了从海洋贝类 中鉴定出的三种新型抗菌肽。通过纳升液相色谱-电喷雾-串联质谱（nanoLC-ESI-MS-MS）技术对肽库进行分析，通过生物信息学预测和选择化学合成和评估其生物活性，鉴定出三种潜在的抗菌肽（Nv-p1、Nv-p2 和 Nv-p3）。数据库搜索表明，其中两种与来自其他无脊椎动物物种的组蛋白 H4 肽片段具有部分同源性。结构预测表明，即使放置在靠近脂质双层斑块的位置，它们都采用无规卷曲结构。Nv-p1、Nv-p2 和 Nv-p3 对 表现出活性。在放射扩散测定中，最有效的肽 Nv-p3 的抑制活性起始浓度为 1.5 µg/mL。这些肽对 、 、 无效。另一方面，这些肽对 、 、 表现出有效的抗生物膜作用，但对浮游细胞无效。在有效抗菌浓度下，这些肽对原代人巨噬细胞和胎儿肺成纤维细胞均无明显毒性。我们的结果表明， 衍生的肽代表新的 AMP 序列，具有被优化并开发成针对细菌和真菌感染的抗生素替代物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/1b1d2a3ef35b/ijms-24-03852-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/868be0b7cae2/ijms-24-03852-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/e06e6bc72ef2/ijms-24-03852-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/184531c0e5fd/ijms-24-03852-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/b6734bd1fc62/ijms-24-03852-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/1b1d2a3ef35b/ijms-24-03852-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/868be0b7cae2/ijms-24-03852-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/e06e6bc72ef2/ijms-24-03852-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/184531c0e5fd/ijms-24-03852-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/b6734bd1fc62/ijms-24-03852-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d7e/9968088/1b1d2a3ef35b/ijms-24-03852-g005.jpg

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