title: TC38, a teleost TFPI-2 peptide that kills bacteria via penetration of the cell membrane and interaction with nucleic acids.
abstract: Tissue factor pathway inhibitor 2 (TFPI-2) is an analog of TFPI-1 and a potent endogenous inhibitor of tissue factor (TF)-mediated blood coagulation. Recent reports have proven that the C-terminal of TFPI-2 peptides in humans and several other vertebrates possesses antibacterial activity against Gram-positive and Gram-negative bacteria. In our previous study, we reported that the TFPI-2 peptide, TC38 in tongue sole (Cynoglossus semilaevis) was active against Micrococcus luteus. In this study, we further examine the antimicrobial spectrum, mechanism of action, and function of TC38 in tongue sole. Our results indicate that TC38 is active against the Gram-negative bacteria Vibrio ichthyoenteri, Vibrio litoralis, Vibrio parahaemolyticus, and Vibrio vulnificus, as well as the fish Megalocytivirus, infectious spleen and kidney necrosis virus (ISKNV). The mechanism of action of TC38 against V. vulnificus was explored. The results showed that TC38 killed V. vulnificus cells without lysis of the cell membrane. FITC-labeled TC38 was able to penetrate the cell membrane and bind to DNA and RNA, then disrupt cellular function, eventually leading to cell death. Administration of TC38 to tongue sole significantly improved its defense against V. vulnificus infection. Overall, these results indicate that TC38 is a novel peptide with a broad antimicrobial spectrum. Furthermore, the unique action of TC38 against V. vulnificus adds new insights to the mechanism of action of vertebrate TFPI peptides. Moreover, TC38 is an interesting antimicrobial agent that could be useful in the fight against pathogenic invasion in aquaculture.
authors.affiliation: Marine Science and Engineering College, Qingdao Agricultural University, Qingdao 266109, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Marine Science and Engineering College, Qingdao Agricultural University, Qingdao 266109, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yue
authors.affiliation: Animal lab, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Zhang
authors.affiliation: Marine Science and Engineering College, Qingdao Agricultural University, Qingdao 266109, China.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Marine Science and Engineering College, Qingdao Agricultural University, Qingdao 266109, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Marine Science and Engineering College, Qingdao Agricultural University, Qingdao 266109, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Marine Science and Engineering College, Qingdao Agricultural University, Qingdao 266109, China. Electronic address: sfcheng@qau.edu.cn.
authors.forename: Shun-Feng
authors.initials: SF
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Fishery Drug Development, Ministry of Agriculture, Key Laboratory of Aquatic Animal Immune Technology, Guangdong Province, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China. Electronic address: liningq@126.com.
authors.forename: Ning-Qiu
authors.initials: NQ
authors.lastname: Li
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000382:microbiology / Q000821:virology; D004266:DNA Virus Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D005393:Fish Diseases / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000821:virology; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D005412:Flatfishes; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D007497:Iridoviridae / Q000502:physiology; D009696:Nucleic Acids / Q000378:metabolism; D011897:Random Allocation; D014733:Vibrio / Q000502:physiology; D014735:Vibrio Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*
chemical_list: D029941:Fish Proteins; D006023:Glycoproteins; D009696:Nucleic Acids; C021240:tissue-factor-pathway inhibitor 2
keywords: Antibacterial activity; Antimicrobial peptide; TFPI-2; Tongue sole