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Fowlicidin‐3 is an α‐helical cationic host defense peptide with potent antibacterial and lipopolysaccharide‐neutralizing activities
Author(s) -
Bommineni Yugendar R.,
Dai Huaien,
Gong YuXi,
Soulages Jose L.,
Fernando Samodha C.,
DeSilva Udaya,
Prakash Om,
Zhang Guolong
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05589.x
Subject(s) - cathelicidin , antimicrobial , antimicrobial peptides , bacteria , lipopolysaccharide , microbiology and biotechnology , biology , peptide , pathogenic bacteria , antibiotics , gram negative bacteria , proinflammatory cytokine , chemistry , biochemistry , escherichia coli , gene , immunology , inflammation , genetics
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 α‐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 µ m . 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 µ m . Fowlicidin‐3 appears to be an excellent candidate for future development as a novel antimicrobial and antisepsis agent, particularly against antibiotic‐resistant pathogens.