Fowlicidin-3 is an α-helical cationic host defense peptide with potent antibacterial and lipopolysaccharide-neutralizing activities

Yugendar R. Bommineni, Huaien Dai, Yu Xi Gong, Jose L. Soulages, Samodha C. Fernando, Udaya DeSilva, Om Prakash, Guolong Zhang

Research output: Contribution to journalArticle

62 Scopus citations

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 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 μm. 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 μm. Fowlicidin-3 appears to be an excellent candidate for future development as a novel antimicrobial and antisepsis agent, particularly against antibiotic-resistant pathogens.

Original languageEnglish (US)
Pages (from-to)418-428
Number of pages11
JournalFEBS Journal
Volume274
Issue number2
DOIs
StatePublished - Jan 1 2007

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Keywords

  • Antibiotic resistance
  • Antimicrobial peptide
  • Cathelicidin
  • Host defense
  • Structure-activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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