Characterization and bioactivity of hepcidin-2 in zebrafish: dependence of antibacterial activity upon disulfide bridges.
Hepcidin is an antimicrobial peptide and iron-regulatory molecule with highly conserved disulfide bridges among vertebrates, but structural insights into the function in fish remains largely missing. We demonstrate here that recombinant hepcidin-2 from zebrafish is capable of inhibiting the growth of the Gram-negative bacteria Escherichia coli and Vibrio anguillarum, and the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis with minimum inhibitory concentrations (MICs) of 18, 15, 13 and 9μM, respectively. We also show by TEM examination that recombinant hepcidin-2 is directly cidal to the cells of E. coli and S. aureus. Moreover, we find that hepcidin-2 displays affinity to LPS, LTA and PGN. All these data indicate that hepcidin-2 is both a pattern recognition molecule, capable of identifying LPS, LTA and PGN, and an antibacterial effector, capable of inhibiting the growth of bacteria. The data also show that the antibacterial activity of hepcidin-2 depends upon the disulfide bridges.
Laboratory for Evolution & Development, Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, Qingdao 266003, China.
Wenjing
W
Lin
Laboratory for Evolution & Development, Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, Qingdao 266003, China.
Shousheng
S
Liu
Laboratory for Evolution & Development, Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, Qingdao 266003, China.
Lili
L
Hu
Laboratory for Evolution & Development, Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, Qingdao 266003, China. Electronic address: sczhang@ouc.edu.cn.
Shicui
S
Zhang
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001412:Bacillus subtilis / Q000187:drug effects / Q000254:growth & development; D004220:Disulfides / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D064451:Hepcidins / Q000008:administration & dosage / Q000235:genetics*; D008070:Lipopolysaccharides / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D015027:Zebrafish / Q000235:genetics* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D004220:Disulfides; D064451:Hepcidins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins
Bactericidal activity; Danio rerio; Hepcidin-2; Zebrafish