Structural and functional characterization of CATH_BRALE, the defense molecule in the ancient salmonoid, Brachymystax lenok

Li, Zheng; Zhang, Songyan; Gao, Jiuxiang; Guang, Huijuan; Tian, Yuanyong; Zhao, Zongmao; Wang, Yipeng; Yu, Haining

doi:10.1016/j.fsi.2012.07.004

Cited by 22 publications

(16 citation statements)

References 28 publications

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“…Homology structure modeling of cathelicidin-RCs was conducted according to the previous paper [20]. The BLAST against PDB protein databank for cathelicidin-RC1 and cathelicidin-RC2 was performed to obtain the most suitable templates.…”

Section: Methodsmentioning

confidence: 99%

Cathelicidins from the Bullfrog Rana catesbeiana Provides Novel Template for Peptide Antibiotic Design

et al. 2014

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Cathelicidins, a class of gene-encoded effector molecules of vertebrate innate immunity, provide a first line of defense against microbial invasions. Although cathelicidins from mammals, birds, reptiles and fishes have been extensively studied, little is known about cathelicidins from amphibians. Here we report the identification and characterization of two cathelicidins (cathelicidin-RC1 and cathelicidin-RC2) from the bullfrog Rana catesbeiana. The cDNA sequences (677 and 700 bp, respectively) encoding the two peptides were successfully cloned from the constructed lung cDNA library of R. catesbeiana. And the deduced mature peptides are composed of 28 and 33 residues, respectively. Structural analysis indicated that cathelicidin-RC1 mainly assumes an amphipathic alpha-helical conformation, while cathelicidin-RC2 could not form stable amphipathic structure. Antimicrobial and bacterial killing kinetic analysis indicated that the synthetic cathelicidin-RC1 possesses potent, broad-spectrum and rapid antimicrobial potency, while cathelicidin-RC2 exhibited very weak antimicrobial activity. Besides, the antimicrobial activity of cathelicidin-RC1 is salt-independent and highly stable. Scanning electron microscopy (SEM) analysis indicated that cathelicidin-RC1 kills microorganisms through the disruption of microbial membrane. Moreover, cathelicidin-RC1 exhibited low cytotoxic activity against mammalian normal or tumor cell lines, and low hemolytic activity against human erythrocytes. The potent, broad-spectrum and rapid antimicrobial activity combined with the salt-independence, high stability, low cytotoxic and hemolytic activities make cathelicidin-RC1 an ideal template for the development of novel peptide antibiotics.

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Section: Methodsmentioning

confidence: 99%

Cathelicidins from the Bullfrog Rana catesbeiana Provides Novel Template for Peptide Antibiotic Design

et al. 2014

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“…Upon sequence analysis of the cDNA that encoded these peptides, it was discovered that they exhibited homology to cathelicidins, previously only found in mammals to this point. As cathelicidins were discovered in other more conventional fish species, primarily by sequence homology from the cathelin region (e.g., [17,28,77,185]), or more recently by peptide isolation [186], new patterns emerged. In some of the more recently studied fish cathelicidins, while a high degree of homology is maintained in the cathelin domain (see [185] for a comprehensive alignment), there appears to be a higher degree of sequence similarity of the mature peptide than seen in mammals.…”

Section: Cathelicidinsmentioning

confidence: 99%

“…For parasites, the minimum protozoacidal concentration (PC min ) or MIC is indicated. Habitat of microorganisms are indicated (freshwater, marine or other).Bacteriaβ-DefensinPiscidinHepcdinCathelicidinHistone-derivedPathogenicHabitatFishHumanGram negative Escherichia coli 39.0 ± 3.7 (vLD 90 ) [60]32.6 ± 1.5 (vLD 90 ) [52]IH [10]5–10 μM (MIC) [50]2–10 μM (MIC) [117]50 μg/mL (MIC) [40]2.2–3.3 μM (MIC) [6]5 μM (MIC) [43]3–6 μM (MIC) [47]2 μg/mL (MIC) [83]3 μM (MIC) [75]1 μg/mL (MIC) [8]5–10 μM (MIC) [23]>96 μM (MIC) [62]6-12 μM (MIC) [171]18.66 (IC 50 ) [36]11 μM (MIC) [161]12–24 μM (MIC) [48]>8.18 μM (MIC) [37]34.56 mm 2 (IH) [49]<1 μg/mL (MIC) [187]1 μg/mL (MIC) [225][20]2–4 μg/mL (MIC) [77]5 μg/mL (MIC) [186]1 μg/mL(MIC) [29]>10 μg/mL(MIC) […”

Section: Table S1mentioning

confidence: 99%

Antimicrobial Peptides from Fish

2014

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Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture.

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“…Some cathelicidinderived AMPs, such as Iseganan, Omiganan and MBI 594AN, have been used in clinical trials, suggesting their good prospects as novel peptide antibiotics [9]. To date, a number of cathelicidins have been identified from most vertebrates including fishes, birds, reptiles and mammals [10][11][12], but there is a noticeable lack of literature regarding cathelicidins in amphibiansa complex group of animals that are highly resistant to infection with microorganisms. In this study, we identified two cathelicidins (Lf-CATH1/2) from the constructed skin cDNA library of the ranid frog, Limnonectes fragilis.…”

Section: Introductionmentioning

confidence: 99%

Identification and polymorphism discovery of the cathelicidins, Lf‐CATHs in ranid amphibian (Limnonectes fragilis)

Cai

Gao

et al. 2013

The FEBS Journal

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To protect themselves against the invasion of microorganisms, amphibians, especially the Rana frogs, are possibly equipped with complex combinations of antimicrobial peptides (AMPs). The two major AMP families, ranid skin secretion AMPs and cathelicidins might together constitute the host innate immune system of amphibians. Cathelicidins are a group of cationic peptides found in leukocytes and epithelial cells, and they play a central role in the early innate immune defense found in virtually all species of mammals. However, they have rarely been reported from amphibians. Here, we report the identification and discovery of polymorphism cathelicidins in Limnonectes fragilis. The expression profile indicated high cathelicidin transcript levels in frog spleen, liver and kidney, but lower levels in lung, skin and stomach. According to the amphibian's unique proteolytic pattern, R125 and L121 of the prepropeptides are predicted to be the processing positions for protease to generate the mature peptides, Lf‐CATH1 and ‐2, respectively. Both consist of 30 amino acid residues, of which two were cysteines positionally conserved among a few known amphibian cathelicidins. Homology modeling analysis revealed that Lf‐CATH1 and ‐2 adopt a tertiary structure with a mostly α helix that is representative of small cationic cathelicidin family peptides. Recombinant Lf‐CATH1 (rLf‐CATH1) was produced in Escherichia coli. Synthetic Lf‐CATH1 and ‐2 displayed potent antimicrobial activities in vitro against a broad spectrum of microorganisms, including standard and clinically isolated drug‐resistant strains, while showing neglectable hemolysis and cytotoxicities.

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Structural and functional characterization of CATH_BRALE, the defense molecule in the ancient salmonoid, Brachymystax lenok

Cited by 22 publications

References 28 publications

Cathelicidins from the Bullfrog Rana catesbeiana Provides Novel Template for Peptide Antibiotic Design

Cathelicidins from the Bullfrog Rana catesbeiana Provides Novel Template for Peptide Antibiotic Design

Antimicrobial Peptides from Fish

Identification and polymorphism discovery of the cathelicidins, Lf‐CATHs in ranid amphibian (Limnonectes fragilis)

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