Host defense peptide LEAP-2 contributes to monocyte/macrophage polarization in barbel steed (Hemibarbus labeo)

Chen, Jie; Lv, Yao-Ping; Dai, Qing-Min; Hu, Zehui; Liu, Zi-Ming; Li, Jiheng

doi:10.1016/j.fsi.2019.01.015

Cited by 28 publications

(12 citation statements)

References 36 publications

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“…The theoretical MW of mature LEAP-2 matched well with the observed MW. The alignment of topmouth culter LEAP-2 precursor with selected cyprinid fish LEAP-2 precursors indicated that there are a conserved “RXXR” amino acid sequence before the cleavage site separating the prodomain and the mature LEAP-2 peptide, a conserved “MTPLWR” amino acid sequence at the N-terminal of mature LEAP-2 peptide, and a conserved “RXGH” amino acid sequence at the C-terminal of mature LEAP-2 peptide as described previously ( Figure 3 ; Chen et al, 2019 ). In addition, the mature LEAP-2 peptide of topmouth culter contains four conserved cysteine residues that form two intramolecular disulfide bonds, and the four cysteine residues are probably linked in Cys1-Cys2 and Cys2-Cys4 patterns as described previously ( Figure 3 ; Chen et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…They share four cysteine residues at conserved positions and even share several conserved amino acid sequences ( Yang et al, 2014 ). The four conserved cysteine residues usually formed two intramolecular disulfide bonds linked in Cys1-Cys3 and Cys-2-Cys4 patterns ( Chen et al, 2019 ). So far, a series of LEAP-2 have been characterized from several fish species, including channel catfish ( Ictalurus punctatus ; Bao et al, 2006 ), grass carp ( Ctenopharyngodon idella ; Liu et al, 2010 ), common carp ( Cyprinus carpio L .…”

Section: Introductionmentioning

confidence: 99%

“…So far, a series of LEAP-2 have been characterized from several fish species, including channel catfish ( Ictalurus punctatus ; Bao et al, 2006 ), grass carp ( Ctenopharyngodon idella ; Liu et al, 2010 ), common carp ( Cyprinus carpio L . ; Yang et al, 2014 ), blunt snout bream ( Megalobrama amblycephala ; Liang et al, 2013 ), rainbow trout ( Oncorhynchus mykiss ; Zhang et al, 2004 ), miiuy croaker ( Miichthys miiuy ; Liu et al, 2014 ), teleost fish ( Plecoglossus altivelis ; Li et al, 2015 ), mudskipper ( Boleophthalmus pectinirostris ; Chen et al, 2016 ), and barbel steed ( Hemibarbus labeo ; Chen et al, 2019 ). LEAP-2 play critical roles in host innate immune response against pathogenic invasion in these fish species ( Yang et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Anti-infective Effects of a Fish-Derived Antimicrobial Peptide Against Drug-Resistant Bacteria and Its Synergistic Effects With Antibiotic

Chen

Cheng

et al. 2020

Front. Microbiol.

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Antimicrobial peptides (AMPs) play pivotal roles in protecting against microbial infection in fish. However, AMPs from topmouth culter (Erythroculter ilishaeformis) are rarely known. In our study, we isolated an AMP from the head kidney of topmouth culter, which belonged to liver-expressed antimicrobial peptide 2 (LEAP-2) family. Topmouth culter LEAP-2 showed inhibitory effects on aquatic bacterial growth, including antibiotic-resistant bacteria, with minimal inhibitory concentration values ranging from 18.75 to 150 μg/ml. It was lethal for Aeromonas hydrophila (resistant to ampicillin), and took less than 60 min to kill A. hydrophila at a concentration of 5 × MIC. Scanning electron microscope (SEM) and SYTOX Green uptake assay indicated that it impaired the integrity of bacterial membrane by eliciting pore formation, thereby increasing the permeabilization of bacterial membrane. In addition, it showed none inducible drug resistance to aquatic bacteria. Interestingly, it efficiently delayed ampicillin-induced drug resistance in Vibrio parahaemolyticus (sensitive to ampicillin) and sensitized ampicillin-resistant bacteria to ampicillin. The chequerboard assay indicated that topmouth culter LEAP-2 generated synergistic effects with ampicillin, indicating the combinational usage potential of topmouth culter LEAP-2 with antibiotics. As expected, topmouth culter LEAP-2 significantly alleviated ampicillin-resistant A. hydrophila infection in vivo, and enhanced the therapeutic efficacy of ampicillin against A. hydrophila in vivo. Our findings provide a fish innate immune system-derived peptide candidate for the substitute of antibiotics and highlight its potential for application in antibiotic-resistant bacterial infection in aquaculture industry.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-infective Effects of a Fish-Derived Antimicrobial Peptide Against Drug-Resistant Bacteria and Its Synergistic Effects With Antibiotic

Chen

Cheng

et al. 2020

Front. Microbiol.

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“…However, unlike mammals with a single LEAP-2 , three LEAP-2s have been discovered in fish species, including LEAP-2A , LEAP-2B and LEAP-2C ( 20 – 23 ), and the tissue expression patterns in different fish species are also different ( 22 , 24 ). Teleost LEAP-2 can enhance the bacterial killing efficiency of monocytes/macrophages ( 25 , 26 ) and has a synergistic effect with antibiotics on the killing of drug-resistant bacteria ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative study on antibacterial characteristics of the multiple liver expressed antimicrobial peptides (LEAPs) in teleost fish

Liu

Hu²,

Pan³

et al. 2023

Front. Immunol.

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Antimicrobial peptides are important components of the host innate immune system, forming the first line of defense against infectious microorganisms. Among them, liver-expressed antimicrobial peptides (LEAPs) are a family of antimicrobial peptides that widely exist in vertebrates. LEAPs include two types, named LEAP-1 and LEAP-2, and many teleost fish have two or more LEAP-2s. In this study, LEAP-2C from rainbow trout and grass carp were discovered, both of which are composed of 3 exons and 2 introns. The antibacterial functions of the multiple LEAPs were systematically compared in rainbow trout and grass carp. The gene expression pattern revealed that rainbow trout and grass carp LEAP-1, LEAP-2A, LEAP-2B and/or LEAP-2C were differentially expressed in various tissues/organs, mainly in liver. After bacterial infection, the expression levels of LEAP-1, LEAP-2A, LEAP-2B and/or LEAP-2C in the liver and gut of rainbow trout and grass carp increased to varying degrees. Moreover, the antibacterial assay and bacterial membrane permeability assay showed that rainbow trout and grass carp LEAP-1, LEAP-2A, LEAP-2B and LEAP-2C all have antibacterial activities against a variety of Gram-positive and Gram-negative bacteria with varying levels through membrane rupture. Furthermore, cell transfection assay showed that only rainbow trout LEAP-1, but not LEAP-2, can lead to the internalization of ferroportin, the only iron exporter on cell surface, indicating that only LEAP-1 possess iron metabolism regulation activity in teleost fish. Taken together, this study systematically compared the antibacterial function of LEAPs in teleost fish and the results suggest that multiple LEAPs can enhance the immunity of teleost fish through different expression patterns and different antibacterial activities to various bacteria.

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“…Furthermore, LEAP2 from C. hamatus contains more certain amino acids, for example Pro residues, which were found to enhance its antibacterial activity (Das et al, 2010). Although LEAP2 was expressed in most tissues, the highest expression was in the liver (Chen et al, 2019; Liang et al, 2013). However, LEAP‐2 transcript expression in channel catfish Ictalurus punctatus was the lowest in the liver among the 11 tested tissues (Bao et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Identification of antibacterial activity of LEAP2 from Antarctic icefish Chionodraco hamatus

Fei

Wang

et al. 2023

Journal of Fish Diseases

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Liver‐expressed antimicrobial peptide 2 (LEAP2) is a small peptide, which is consisted of signal peptide, pro‐peptide and the bioactive mature peptide. Mature LEAP2 is an antibacterial peptide with four highly conserved cysteines forming two intramolecular disulfide bonds. Chionodraco hamatus, an Antarctic notothenioid fish that lives in the coldest water, has white blood unlike most fish of the world. In this study, the LEAP2 coding sequence was cloned from C. hamatus, including a 29 amino acids signal peptide and mature peptide of 46 amino acids. High levels of LEAP2 mRNA were detected in the skin and liver. Mature peptide was obtained by chemical synthesis in vitro, displayed selective antimicrobial activities against Escherichia coli, Aeromonas hydrophila, Staphylococcus aureus and Streptococcus agalactiae. Liver‐expressed antimicrobial peptide 2 showed bactericidal activity by destroying the cell membrane integrity and robustly combined with bacterial genomic DNA. In addition, overexpression of the Tol‐LEAP2‐EGFP in zebrafish larva showed stronger antimicrobial activity in C. hamatus than in zebrafish, accompanied by lower bacterial load and expression of pro‐inflammatory factors. This is the first demonstration of the antimicrobial activity of LEAP2 from C. hamatus, which is of useful value in improving resistance to pathogens.

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Host defense peptide LEAP-2 contributes to monocyte/macrophage polarization in barbel steed (Hemibarbus labeo)

Cited by 28 publications

References 36 publications

Anti-infective Effects of a Fish-Derived Antimicrobial Peptide Against Drug-Resistant Bacteria and Its Synergistic Effects With Antibiotic

Anti-infective Effects of a Fish-Derived Antimicrobial Peptide Against Drug-Resistant Bacteria and Its Synergistic Effects With Antibiotic

Comparative study on antibacterial characteristics of the multiple liver expressed antimicrobial peptides (LEAPs) in teleost fish

Identification of antibacterial activity of LEAP2 from Antarctic icefish Chionodraco hamatus

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