title: Molecular characterization of a novel hepcidin (HepcD) from Camelus dromedarius. Synthetic peptide forms exhibit antibacterial activity.
abstract: Hepcidin is a cysteine-rich peptide widely characterized in immunological processes and antimicrobial activity in several vertebrate species. Obviously, this hormone plays a central role in the regulation of systemic iron homeostasis. However, its role in camelids' immune response and whether it is involved in antibacterial immunity have not yet been proven. In this study, we characterized the Arabian camel hepcidin nucleotide sequence with an open reading frame of 252 bp encoding an 83-amino acid preprohepcidin peptide. Eight cysteine key residues conserved in all mammalian hepcidin sequences were identified. The model structure analysis of hepcidin-25 peptide showed a high homology structure and sequence identity to the human hepcidin. Two different hepcidin-25 analogs manually synthesized by SPPS shared significant cytotoxic capacity toward the Gram-negative bacterium Escherichia coli American Type Culture Collection (ATCC) 8739 as well as the Gram-positive bacteria Bacillus subtilis ATCC 11779 and Staphylococcus aureus ATCC 6538 in vitro. The three disulfide bridges hepcidin analog demonstrated bactericidal activity, against B. subtilis ATCC 11779 and S. aureus ATCC 6538 strains, at the concentration of 15 μM (50 µg/ml) or above at pH 6.2. This result correlates with the revealed structural features suggesting that camel hepcidin is proposed to be involved in antibacterial process of innate immune response.
authors.affiliation: Laboratoire d'ingénierie des protéines et des molécules bioactives, Institut National des Sciences Appliquées et de Technologie, Université de Carthage, BP 676, 1080, Tunis Cedex, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Boumaiza
authors.forename: Aymen
authors.initials: A
authors.lastname: Ezzine
authors.forename: Maryse
authors.initials: M
authors.lastname: Jaouen
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Sari
authors.forename: Mohamed Nejib
authors.initials: MN
authors.lastname: Marzouki
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000254:growth & development*; D001483:Base Sequence; D002162:Camelus; D003001:Cloning, Molecular; D004220:Disulfides / Q000737:chemistry; D064451:Hepcidins / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames
chemical_list: D000900:Anti-Bacterial Agents; D004220:Disulfides; D064451:Hepcidins
keywords: Camelus dromedarius; MTT reduction test; antimicrobial activity; hepcidin cDNA; hepcidin-25 analogs