Hamp Type-1 Promotes Antimicrobial Defense via Direct Microbial Killing and Regulating Iron Metabolism in Grass Carp (Ctenopharyngodon idella).

Yazhen Hu,Yong-An Zhang,Gailing Yuan,Tomofumi Kurobe,Xiaoling Liu,Jianguo Su

doi:10.3390/biom10060825

Yazhen Hu, Yong-An Zhang + Show 4 more

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https://doi.org/10.3390/biom10060825

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Abstract

Hepcidin is an antimicrobial peptide and regulator of iron homeostasis which has two isoforms in most fishes and some mammals. Previous studies have reported that the two hepcidin isoforms have different roles. Hamp type-1 plays a regulatory role in iron metabolism and hamp type-2 mostly performs an antimicrobial role. In this study, we found that Ctenopharyngodon idella (C. idella) have only one hepcidin isoform (hamp type-1), which showed both broad-spectrum antibacterial and iron regulatory functions. C. idella hepcidin mature peptide (hepcidin-25) and truncated peptide (hepcidin-20) exhibited bactericidal activities against both Gram-positive and Gram-negative bacteria in a dose-dependent manner in part through membrane rupture and binding to bacterial genomic DNA. The data from challenge tests demonstrated that the administration of hepcidin-25 significantly reduced mortality rates of C. idella by A. hydrophila infection, probably due to direct bactericidal activities of the peptide and a reduction of iron content in the fish serum. In addition, a comparison between hepcidin-20 and -25 suggests that the N terminal 5 amino acids play a critical role in reducing iron content in fish serum. Our findings revealed an important role of hamp type-1 in maintaining iron homeostasis and fighting against bacterial infections, suggesting the hepcidin has implications for the prevention and control of bacterial infection in aquaculture.

Highlights

Hepcidin is a cysteine-rich iron regulating peptide with a predicted complex disulfide pattern [1,2]
Prediction of the tertiary structure revealed that the grass carp hepcidin consists of N-terminal (5-AA) and β-sheet (20-AA), which can lead to hydrophilic cluster formation and surface exposure of the cationic residues (Figure 1A,B)
Our finding demonstrated that the grass carp has only one hepcidin, which is involved in both iron homeostasis regulation and bacteria-killing

Summary

Introduction

Hepcidin is a cysteine-rich iron regulating peptide with a predicted complex disulfide pattern [1,2]. Hepcidin exhibits strong bactericidal activity against various Gram-negative and Gram-positive bacteria [4,5]. Hepcidin was found to be a multifunctional molecule that plays an important role in maintaining iron homeostasis as well [6]. Hepcidin plays a critical role in host defense system against bacterial infections by inducing reactive hypoferremia during early phases of infection [7,8]. Hepcidin triggers iron efflux protein Ferroportin (Fpn) polyubiquitination and induces its internalization. These reactions result in the blocking of cellular iron efflux and reduce the available iron content of extracellular pathogens [6,11,12,13]. Iron removal regulated by hepcidin is an important strategy for controlling bacterial growth and survival

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