title: The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss.
abstract: Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15-20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N- nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-20-27) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(1-15-20-27) could be a promising antimicrobial agent for clinical application.
authors.affiliation: College of Animal Science and Technology, Northeast Agricultural University, Harbin, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Qu
authors.affiliation: College of Animal Science and Technology, Northeast Agricultural University, Harbin, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: College of Animal Science and Technology, Northeast Agricultural University, Harbin, People's Republic of China.
authors.forename: Huixian
authors.initials: H
authors.lastname: Chen
authors.affiliation: College of Animal Science and Technology, Northeast Agricultural University, Harbin, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Northeast Agricultural University, Harbin, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: College of Animal Science and Technology, Northeast Agricultural University, Harbin, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Animal Science and Technology, Northeast Agricultural University, Harbin, People's Republic of China fengxingjun@neau.edu.cn liuchunlong1976@163.com.
authors.forename: Xingjun
authors.initials: X
authors.lastname: Feng
authors.affiliation: Northeast Institute of Geography and Agricultural Ecology, Chinese Academy of Sciences, Harbin, People's Republic of China Collaborative Innovation Center for Development and Utilization of Forest Resources, Harbin, People's Republic of China fengxingjun@neau.edu.cn liuchunlong1976@163.com.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Animal Husbandry Research Centre of Heilongjiang Academy of Agricultural Science, Harbin, People's Republic of China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002645:Chickens; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C517780:fowlicidin-3, chicken