首个对脓毒症小鼠有有效治疗作用的海豹抗菌肽的鉴定

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-03-25 DOI:10.1016/j.bcp.2025.116891

Jiali Li , Weichen Xiong , Jianxi Yang , Weifei Liao , Yihan Gao , Jinwei Chai , Jiena Wu , Shuwen Liu , Xueqing Xu

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引用次数: 0

摘要

海洋生物是天然生物活性物质的宝贵来源，越来越多的海洋抗菌肽作为抗生素的潜在替代品正在开发中。然而，南极哺乳动物抗菌肽的研究尚未见报道。在此背景下，我们从南极哺乳动物weddellileptonychotes全基因组数据库中鉴定出一种抗菌肽cth - lw （rlrdlirrgrqkigrrrinrlgrriqdilknlqpgkvs）。Cath-LW具有典型的α-螺旋结构和广谱抗菌活性。此外，还发现Cath-LW通过破坏细胞膜、结合细菌基因组、抑制DNA功能来发挥抗菌作用。此外，Cath-LW还能中和脂多糖（LPS），抑制LPS诱导的炎症反应。有趣的是，Cath-LW还显示出抗凝血活性，并抑制fecl3诱导的小鼠颈动脉血栓形成。最后，在脓毒症小鼠中，通过有效减轻器官炎症和损伤以及血栓形成，证明了cat - lw可以提高存活率。这些发现不仅加深了我们对韦氏乳杆菌抵抗微生物感染的生存策略的理解，而且为开发新型多功能抗败血症药物提供了重要的模板。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Characterization of the first antimicrobial peptide from Sea Seal with potent therapeutic effect in septic mice

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Characterization of the first antimicrobial peptide from Sea Seal with potent therapeutic effect in septic mice

Marine organisms are a valuable source of natural bioactive substances, and an increasing number of marine antimicrobial peptides as the potential alternative to antibiotics are being developed. Nonetheless, antimicrobial peptides from Antarctic mammals have not been reported heretofore. In this context, we identified a Cathelicidin antimicrobial peptide, Cath-LW (RLRDLIRRGRQKIGRRINRLGRRIQDILKNLQPGKVS), from the whole-genome database of Leptonychotes weddellii, an Antarctic mammal. Cath-LW was characterized to exhibit a typical α-helix structure and broad-spectrum antimicrobial activity. Furthermore, Cath-LW was found to exert its antibacterial effect by destroying cytomembrane, binding to bacterial genome, and inhibiting DNA function. Additionally, Cath-LW could neutralize lipopolysaccharide (LPS) and inhibit LPS-induced inflammatory responses. Interestingly, Cath-LW also showed anticoagulant activity and suppressed FeCl₃-induced carotid thrombosis in mice. Finally, in septic mice, Cath-LW was demonstrated to improve the survival rate by effectively alleviating organ inflammation and damage, as well as thrombus formation. These findings not only deepen our understanding of the survival strategies of L. weddellii against microbial infections but also provide a crucial template for developing a novel multifunctional anti-sepsis drug.

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.