FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis
Sepsis is an exacerbated inflammatory reaction induced by severe infection. As important defensive molecules in innate immunity, several AMPs are reported to prevent septic shock. In this study, we characterized a novel cathelicidin, FM-CATH, from the frog skin of F. multistriata. FM-CATH was found...
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Frontiers Media S.A.
2021-08-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.731056/full |
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author | Jiena Wu Jiena Wu Haiyun Zhang Xiaoxin Chen Jinwei Chai Yunrui Hu Weichen Xiong Wancheng Lu Maolin Tian Xin Chen Xueqing Xu |
author_facet | Jiena Wu Jiena Wu Haiyun Zhang Xiaoxin Chen Jinwei Chai Yunrui Hu Weichen Xiong Wancheng Lu Maolin Tian Xin Chen Xueqing Xu |
author_sort | Jiena Wu |
collection | DOAJ |
description | Sepsis is an exacerbated inflammatory reaction induced by severe infection. As important defensive molecules in innate immunity, several AMPs are reported to prevent septic shock. In this study, we characterized a novel cathelicidin, FM-CATH, from the frog skin of F. multistriata. FM-CATH was found to adopt an amphipathic α-helix structural in membrane-mimetic environments and possess favorable antimicrobial effects against bacteria and fungus. In addition, it triggered the agglutination of bacteria. It could also strongly bind to LPS and LTA. Additionally, FM-CATH affected the enzymatic activities of thrombin, plasmin, β-tryptase, and tPA, leading to coagulation inhibition in vitro and in vivo. Finally, we observed that FM-CATH improved survival rate and inhibited pathological alteration, bacterial count, serum biochemistry, and pro-inflammatory cytokine expression in the cecal ligation and puncture-induced sepsis mice. Taken together, these findings suggest that FM-CATH might be served as a promising agent for the treatment of sepsis. |
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spelling | doaj.art-c4b5af2d90df4df6863722a4d02454782022-12-21T22:09:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.731056731056FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced SepsisJiena Wu0Jiena Wu1Haiyun Zhang2Xiaoxin Chen3Jinwei Chai4Yunrui Hu5Weichen Xiong6Wancheng Lu7Maolin Tian8Xin Chen9Xueqing Xu10Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaSepsis is an exacerbated inflammatory reaction induced by severe infection. As important defensive molecules in innate immunity, several AMPs are reported to prevent septic shock. In this study, we characterized a novel cathelicidin, FM-CATH, from the frog skin of F. multistriata. FM-CATH was found to adopt an amphipathic α-helix structural in membrane-mimetic environments and possess favorable antimicrobial effects against bacteria and fungus. In addition, it triggered the agglutination of bacteria. It could also strongly bind to LPS and LTA. Additionally, FM-CATH affected the enzymatic activities of thrombin, plasmin, β-tryptase, and tPA, leading to coagulation inhibition in vitro and in vivo. Finally, we observed that FM-CATH improved survival rate and inhibited pathological alteration, bacterial count, serum biochemistry, and pro-inflammatory cytokine expression in the cecal ligation and puncture-induced sepsis mice. Taken together, these findings suggest that FM-CATH might be served as a promising agent for the treatment of sepsis.https://www.frontiersin.org/articles/10.3389/fphar.2021.731056/fullantimicrobial peptidecathelicidinsepsislipopolysaccharide and lipoteichoic acid-neutralizingcoagulationcecal ligation and puncture |
spellingShingle | Jiena Wu Jiena Wu Haiyun Zhang Xiaoxin Chen Jinwei Chai Yunrui Hu Weichen Xiong Wancheng Lu Maolin Tian Xin Chen Xueqing Xu FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis Frontiers in Pharmacology antimicrobial peptide cathelicidin sepsis lipopolysaccharide and lipoteichoic acid-neutralizing coagulation cecal ligation and puncture |
title | FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis |
title_full | FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis |
title_fullStr | FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis |
title_full_unstemmed | FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis |
title_short | FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis |
title_sort | fm cath a novel cathelicidin from fejervarya multistriata shows therapeutic potential for treatment of clp induced sepsis |
topic | antimicrobial peptide cathelicidin sepsis lipopolysaccharide and lipoteichoic acid-neutralizing coagulation cecal ligation and puncture |
url | https://www.frontiersin.org/articles/10.3389/fphar.2021.731056/full |
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