Bass hepcidin synthesis, solution structure, antimicrobial activities and synergism, and in vivo hepatic response to bacterial infections

Lauth, X; Babon, JJ; Stannard, JA; Singh, S; Nizet, V; Carlberg, JM; Ostland, VE; Pennington, MW; Norton, RS; Westerman, ME

Author(s): Lauth, X; Babon, JJ; Stannard, JA; Singh, S; Nizet, V; Carlberg, JM; Ostland, VE; Pennington, MW; Norton, RS; Westerman, ME;
Details: Publication Year 2005-03-11,Volume 280,Issue #10,Page 9272-9282
Journal Title: JOURNAL OF BIOLOGICAL CHEMISTRY
Publication Type: Journal Article
Abstract: Bass hepcidin was purified from the gill of hybrid striped bass ( Morone chrysops x Morone saxatilis) based on antimicrobial activity against Escherichia coli. This 21-amino acid peptide has 8 cysteines engaged in 4 disulfide bonds and is very similar to human hepcidin, an antimicrobial peptide with iron regulatory properties. To gain insight into potential role(s) of bass hepcidin in innate immunity in fish, we synthesized the peptide, characterized its antimicrobial activities in vitro, determined its solution structure by NMR, and quantified hepatic gene expression in vivo following infection of bass with the fish pathogens, Streptococcus iniae or Aeromonas salmonicida. Its structure is very similar to that of human hepcidin, including the presence of an antiparallel beta-sheet, a conserved disulfide-bonding pattern, and a rare vicinal disulfide bond. Synthetic bass hepcidin was active in vitro against Gram- negative pathogens and fungi but showed no activity against key Gram- positive pathogens and a single yeast strain tested. Hepcidin was non-hemolytic at microbicidal concentrations and had lower specific activity than moronecidin, a broad spectrum, amphipathic, alpha-helical, antimicrobial peptide constitutively expressed in bass gill tissue. Good synergism between the bacterial killing activities of hepcidin and moronecidin was observed in vitro. Hepcidin gene expression in bass liver increased significantly within hours of infection with Gram- positive ( S. iniae) or Gram- negative ( A. salmonicida) pathogens and was 4 - 5 orders of magnitude above base-line 24-48 h post-infection. Our results suggest that hepcidin plays a key role in the antimicrobial defenses of bass and that its functions are potentially conserved between fish and human.
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Keywords: PEPTIDE ANTIBIOTICS; HEREDITARY HEMOCHROMATOSIS; ACTIVE-SITE; JUVENILE HEMOCHROMATOSIS; METHANOL DEHYDROGENASE; DISULFIDE BRIDGE; SELF-ASSOCIATION; GENE-EXPRESSION; CHRONIC DISEASE; IRON OVERLOAD
Publisher's Version: https://doi.org/10.1074/jbc.M411154200
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2005-03-11 12:00:00