title: Insights into the membrane interaction mechanism and antibacterial properties of chensinin-1b.
abstract: Antimicrobial peptides (AMPs) with non-specific membrane disrupting activities are thought to exert their antimicrobial activity as a result of their cationicity, hydrophobicity and α-helical or β-sheet structures. Chensinin-1, a native peptide from skin secretions of Rana chensinensis, fails to manifest its desired biological properties because its low hydrophobic nature and an adopted random coil structure in a membrane-mimetic environment. In this study, chensinin-1b was designed by rearranging the amino acid sequence of its hydrophilic/polar residues on one face and its hydrophobic/nonpolar residues on the opposite face according to its helical diagram, and by replacing three Gly residues with three Trp residues. Introduction of Trp residues significantly promoted the binding of the peptide to the bacterial outer membrane and exerted bactericidal activity through cytoplasmic membrane damage. Chensinin-1b demonstrates higher antimicrobial activity and greater cell selectivity than its parent peptide, chensinin-1. The electrostatic interactions between chensinin-1b and lipopolysaccharide (LPS) may have facilitated the uptake of the peptide into Gram-negative cells and be also helpful to disrupt the bacterial cytoplasmic membrane, as evidenced by depolarisation of the membrane potential and leakage of calceins from the liposomes of Escherichia coli and Staphylococcus aureus. Chensinin-1b was also found to penetrate mouse skin and was also effective in vivo, as measured by hydroxyproline levels in a wound infection mouse model, and could therefore act as an anti-infective agent for wound healing.
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China; Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China.
authors.forename: Weibing
authors.initials: W
authors.lastname: Dong
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Ma
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China; Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China. Electronic address: djshang@lnnu.edu.cn.
authors.forename: Dejing
authors.initials: D
authors.lastname: Shang
mesh_terms: D020106:Acrylamide / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011193:Potassium Iodide / Q000737:chemistry; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D005452:Fluoresceins; D008070:Lipopolysaccharides; D008081:Liposomes; D010455:Peptides; C000600263:chensinin-1b; D011193:Potassium Iodide; D020106:Acrylamide; D014364:Tryptophan; C007740:fluorexon
keywords: Antimicrobial peptide; Cell selectivity; Depolarization; Lipopolysaccharide; Wound infection