Characterization of a novel LTA/LPS-binding antimicrobial and anti-inflammatory temporin peptide from the skin of Fejervary limnocharis (Anura: Ranidae)

IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Jinqiao Li , Yan Liang , Minhong Su , Jiena Wu , Jinwei Chai , Weichen Xiong , Guoxiang Mo , Xin Chen , Xueqing Xu
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引用次数: 1

Abstract

Septic shock caused by Gram-positive bacteria continues to be a major cause of morbidity and mortality in intensive care units globally. Most Temporins are excellent growth inhibitors of gram-positive bacteria and candidates for developing antimicrobial treatments due to their biological action and small molecular weight. In this study, a novel Temporin peptide from the skin of Fejervarya limnocharis frog, named as Temporin-FL, was characterized. Temporin-FL was found to adopt typical α-helical conformation in SDS solution and to exhibit selective antibacterial activity against Gram-positive bacteria through a membrane destruction mechanism. Accordingly, Temporin-FL showed protective effects against Staphylococcus aureus-induced sepsis in mice. Finally, Temporin-FL was demonstrated to exert anti-inflammatory effects by neutralizing the action of LPS/LTA and by inhibiting MAPK pathway activation. Therefore, Temporin-FL represents a novel candidate for molecular therapy of Gram-positive bacterial sepsis.

Abstract Image

一种新型LTA/ lps结合的颞肽抗菌抗炎肽的鉴定(无尾目:貂科)
革兰氏阳性菌引起的败血症休克仍然是全球重症监护室发病率和死亡率的主要原因。大多数Temporins是革兰氏阳性菌的优秀生长抑制剂,由于其生物作用和小分子量,是开发抗菌治疗方法的候选者。本研究从蛙皮中提取了一种新的Temporin肽,命名为Temporin-FL。Temporin-FL在SDS溶液中采用典型的α-螺旋构象,并通过膜破坏机制对革兰氏阳性菌表现出选择性抗菌活性。因此,Temporin-FL对金黄色葡萄球菌诱导的小鼠败血症显示出保护作用。最后,Temporin-FL通过中和LPS/LTA的作用和抑制MAPK通路的激活而发挥抗炎作用。因此,Temporin-FL为革兰氏阳性细菌败血症的分子治疗提供了一种新的候选药物。
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来源期刊
Biochemical pharmacology
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.
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