title: Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism.
abstract: Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized previously. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids, and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic α-helical conformation in bacterial membrane-mimetic solutions. It possesses potent broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells. The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. In addition, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Hc-CATH directly binds with LPS to neutralize its toxicity, and it also binds to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake discovered to have both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics.
authors.affiliation: the Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wei
authors.affiliation: the Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116023, China.
authors.forename: Jiuxiang
authors.initials: J
authors.lastname: Gao
authors.affiliation: the Binzhou Medical University of Pharmaceutical College, Yantai, Shandong 264003, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: the Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116023, China.
authors.forename: Sijin
authors.initials: S
authors.lastname: Wu
authors.affiliation: the Binzhou Medical University of Pharmaceutical College, Yantai, Shandong 264003, China.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Xie
authors.affiliation: the Cancer Immunology and Immunotherapy Center, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, China, and.
authors.forename: Guiying
authors.initials: G
authors.lastname: Ling
authors.affiliation: the Center for Translational Medicine, Huaihe Clinical Institute, Henan University, Kaifeng, Henan 475000, China.
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Kuang
authors.affiliation: the Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116023, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: the Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116023, China, yuhaining@dlut.edu.cn.
authors.forename: Haining
authors.initials: H
authors.lastname: Yu
authors.affiliation: From the Department of Pharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China, yipengwang@suda.edu.cn.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001483:Base Sequence; D054804:Cathelicidins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017815:Elapidae / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D014714:Vertebrates / Q000145:classification / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D054804:Cathelicidins
keywords: Hc-CATH; Hydrophis cyanocinctus; anti-inflammatory; antibiotics; antimicrobial peptide (AMP); cathelicidin; infection; inflammation; innate immunity