The Era of Antimicrobial Peptides: Use of Hepcidins to Prevent or Treat Bacterial Infections and Iron Disorders

Abstract

The current treatments applied in aquaculture to limit disease dissemination are mostly based on the use of antibiotics, either as prophylactic or therapeutic agents, with vaccines being available for a limited number of fish species and pathogens. Antimicrobial peptides are considered as promising novel substances to be used in aquaculture, due to their antimicrobial and immunomodulatory activities. Hepcidin, the major iron metabolism regulator, is found as a single gene in most mammals, but in certain fish species, including the European sea bass (Dicentrarchus labrax), two different hepcidin types are found, with specialized roles: the single type 1 hepcidin is involved in iron homeostasis trough the regulation of ferroportin, the only known iron exporter; and the various type 2 hepcidins present antimicrobial activity against a number of different pathogens. In this study, we tested the administration of sea bass derived hepcidins in models of infection and iron overload. Administration with hamp2 substantially reduced fish mortalities and bacterial loads, presenting itself as a viable alternative to the use of antibiotics. On the other hand, hamp1 seems to attenuate the effects of iron overload. Further studies are necessary to test the potential protective effects of hamp2 against other pathogens, as well as to understand how hamp2 stimulate the inflammatory responses, leading to an increased fish survival upon infection.

Characterization of Erythroferrone in a Teleost Fish (Dicentrarchus labrax) With Two Functional Hepcidin Types: More Than an Erythroid Regulator

“…During the experimental infection, we observed a huge increase of hamp2 expression that is kept elevated throughout the study, an expected result considering its known antimicrobial role (21,22,44). However, the increases in hamp1 expression are much more limited, mostly to the initial stages of infection, and do not fully mirror the decreases in epo and especially erfe, which are more prolonged.…”

“…However, the increases in hamp1 expression are much more limited, mostly to the initial stages of infection, and do not fully mirror the decreases in epo and especially erfe, which are more prolonged. Nevertheless, the early days suppression of erfe may contribute to the observed hamp1 increases, leading to a limitation in iron availability essential to control the siderophore producing P. damselae proliferation (44), and thus to the early onset of anemia of inflammation. Later recoveries of erfe, as well as epo and hbb, to normal levels of expression, seem to match the recovery from anemia (45), although hamp1 levels do not change significantly.…”

Integration of host-pathogen functional genomics data into the chromosome-level genome assembly of turbot (Scophthalmus maximus)

“…It was also upregulated in spleen after AS, PD and ES challenges. Furthermore, this gene has been reported to be involved in resistance to bacterial infection (Rodrigues et al, 2006) and used for treatment against bacterial infections and iron disorders (Barroso et al, 2021) in Dicentrarchus labrax. Plg is a key activator of the inflammatory response, which facilitates leukocyte recruitment in the site of infection, as well as coagulation, and has been reported in response against Paramoeba perurans in Atlantic salmon (McCormack et al, 2021).…”

Immune Modulation Ability of Hepcidin from Teleost Fish

“…Studies on hepcidin in teleost fish have confirmed the relevance of the molecule in the defense system against pathogenic microorganisms [ 5 , 6 ]. In line with these studies, research in our laboratory has shown that two hepcidin variants from rainbow trout ( Oncorhynchus mykiss ) possess antimicrobial activity against important salmonid pathogens such as Piscirickettsia salmonis .…”