title: Fowlicidin-3 is an alpha-helical cationic host defense peptide with potent antibacterial and lipopolysaccharide-neutralizing activities.
abstract: Cathelicidins are an important family of cationic host defense peptides in vertebrates with both antimicrobial and immunomodulatory activities. Fowlicidin-1 and fowlicidin-2 are two newly identified chicken cathelicidins with potent antibacterial activities. Here we report structural and functional characterization of the putatively mature form of the third chicken cathelicidin, fowlicidin-3, for exploration of its therapeutic potential. NMR spectroscopy revealed that fowlicidin-3 comprises 27 amino-acid residues and adopts a predominantly alpha-helical structure extending from residue 9 to 25 with a slight kink induced by a glycine at position 17. It is highly potent against a broad range of Gram-negative and Gram-positive bacteria in vitro, including antibiotic-resistant strains, with minimum inhibitory concentrations in the range 1-2 microM. It kills bacteria quickly, permeabilizing cytoplasmic membranes immediately on coming into contact with them. Unlike many other host defense peptides with antimicrobial activities that are diminished by serum or salt, fowlicidin-3 retains bacteria-killing activities in the presence of 50% serum or physiological concentrations of salt. Furthermore, it is capable of suppressing lipopolysaccharide-induced expression of proinflammatory genes in mouse macrophage RAW264.7 cells, with nearly complete blockage at 10 microM. Fowlicidin-3 appears to be an excellent candidate for future development as a novel antimicrobial and antisepsis agent, particularly against antibiotic-resistant pathogens.
authors.affiliation: Department of Animal Science, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Yugendar R
authors.initials: YR
authors.lastname: Bommineni
authors.forename: Huaien
authors.initials: H
authors.lastname: Dai
authors.forename: Yu-Xi
authors.initials: YX
authors.lastname: Gong
authors.forename: Jose L
authors.initials: JL
authors.lastname: Soulages
authors.forename: Samodha C
authors.initials: SC
authors.lastname: Fernando
authors.forename: Udaya
authors.initials: U
authors.lastname: Desilva
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.forename: Guolong
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002412:Cations; D004285:Dogs; D007249:Inflammation; D008070:Lipopolysaccharides / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D023083:beta-Defensins / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D002412:Cations; D008070:Lipopolysaccharides; D010455:Peptides; D023083:beta-Defensins; C517780:fowlicidin-3, chicken