An antimicrobial peptide from the skin secretions of the mountain chicken frog Leptodactylus fallax (Anura:Leptodactylidae)

Rollins‐Smith, Louise A.; King, Jay D.; Nielsen, Per F.; Sonnevend, Ágnes; Conlon, J. Michael

doi:10.1016/j.regpep.2004.07.013

Cited by 47 publications

(45 citation statements)

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“…One of the most important innate defenses of amphibian skin is the array of antimicrobial peptides secreted into the mucus. Previous studies have demonstrated that antimicrobial skin peptides from many amphibian species can inhibit B. dendrobatidis growth in vitro (11,(44)(45)(46)(47)(48)(49)(50)(51)(52)(66)(67)(68). We showed in the present study that natural peptide mixtures in the skin secretions of X. laevis also potently inhibited the growth of B. dendrobatidis zoospores.…”

Section: Discussionsupporting

confidence: 70%

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

et al. 2010

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Batrachochytrium dendrobatidis is a chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians. It is regarded as an emerging infectious disease affecting diverse amphibian populations in many parts of the world. Because there are few model amphibian species for immunological studies, little is known about immune defenses against B. dendrobatidis. We show here that the South African clawed frog, Xenopus laevis, is a suitable model for investigating immunity to this pathogen. After an experimental exposure, a mild infection developed over 20 to 30 days and declined by 45 days postexposure. Either purified antimicrobial peptides or mixtures of peptides in the skin mucus inhibited B. dendrobatidis growth in vitro. Skin peptide secretion was maximally induced by injection of norepinephrine, and this treatment resulted in sustained skin peptide depletion and increased susceptibility to infection. Sublethal X-irradiation of frogs decreased leukocyte numbers in the spleen and resulted in greater susceptibility to infection. Immunization against B. dendrobatidis induced elevated pathogen-specific IgM and IgY serum antibodies. Mucus secretions from X. laevis previously exposed to B. dendrobatidis contained significant amounts of IgM, IgY, and IgX antibodies that bind to B. dendrobatidis. These data strongly suggest that both innate and adaptive immune defenses are involved in the resistance of X. laevis to lethal B. dendrobatidis infections.Batrachochytrium dendrobatidis is a newly described chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians (29). Growing evidence links amphibian declines in Australia, Central America, the western United States, Europe, and Africa to this emerging infectious disease (4, 9, 12, 26, 29, 34-36, 45, 65). B. dendrobatidis colonizes skin cells of adults and the keratinized mouth parts of tadpoles (3, 4, 29, 34) but does not invade other tissues. It is spread by waterborne zoospores that attach to the skin and migrate to the basal layer of the epidermis (3). The pathogen replicates within the epidermal cells and moves to the surface as the cells mature. Emerging zoospores may infect the same host or another nearby host (3,4,29,34). Recent evidence supports the hypothesis that death results from impaired retention of essential ions by the skin resulting in eventual cardiac arrest (63, 64). Some species of amphibians are very resistant to lethal infections of B. dendrobatidis, whereas others are more susceptible (4,26,27,38,(66)(67)(68), and the factors that determine resistance or susceptibility are not well understood. Although much is known about amphibian immunity in general (9, 14, 41), there is limited information about specific immune responses against B. dendrobatidis.We hypothesized that resistant species have antimicrobial peptides or antibodies in the mucus that limit initial infections by B. dendrobatidis zoospores and prevent the further colonization of the same host by zoospores emerging from the skin. Previous work has shown th...

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Section: Discussionsupporting

confidence: 70%

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

et al. 2010

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“…The peptide has been termed laticeptin. This work complements previous investigations from the laboratory that led to the characterization of the structurally related antimicrobial peptides, fallaxin from the skin secretions of the Caribbean mountain chicken frog L. fallax [13], and pentadactylin from the South American bullfrog L. pentadactylus [14].…”

Section: Introductionsupporting

confidence: 69%

Purification and Properties of Laticeptin, an Antimicrobial Peptide from Skin Secretions of the South American Frog Leptodactylus laticeps

Conlon¹,

Al-Ghaferi²,

Abraham³

et al. 2006

PPL

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Norepinephrine-stimulated skin secretions from the Sante Fe frog Leptodactylus laticeps contained high concentrations of a peptide, termed laticeptin, with the primary structure Gly-Val-Val-Asp-Ile-Leu-Lys-Gly-Ala-Ala-Lys-Asp-Leu-Ala-Gly-His-Leu-Ala-Thr-Lys-Val-Met-Asn-Lys-Leu.NH(2). Laticeptin inhibited the growth of selected Gram-negative bacteria but the lack of activity against Gram-positive bacteria and the very low hemolytic activity is probably a consequence of the weak amphipathicity of the peptide in its alpha-helical conformation.

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“…Unfortunately, all the truncated analogs showed MIC values >100 mM for all bacterial strains tested. Although, Rollins-Smith et al (2005) found fallaxin 1-22 to be inactive against E. coli and S. aureus at concentrations up to 160 mM, the lack of any activity or selectivity for either bacterial or mammalian cells was quite surprising to us. Our result may be explained by the RP-HPLC retention times, mean hydrophobicity AEHae, and mean hydrophobic moment of these peptides as described in the sections below.…”

Section: C-and N-terminus Truncationsmentioning

confidence: 86%

“…As the assays are sensitive to environmental parameters and since Rollins-Smith et al (2005) used different bacterial strains from this study, the divergent results are most likely to be related to these matters. We found the hemolytic activity of fallaxin to be 0% at a peptide concentration of 50 mM, which is in full accordance with Rollins-Smith et al (2005).…”

Section: Antibacterial Activity Of Fallaxin and Analogsmentioning

confidence: 99%

Structure–activity study of the antibacterial peptide fallaxin

et al. 2007

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Fallaxin is a 25-mer antibacterial peptide amide, which was recently isolated from the West Indian mountain chicken frog Leptodactylus fallax. Fallaxin has been shown to inhibit the growth of several Gram-negative bacteria including Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Here, we report a structure-activity study of fallaxin based on 65 analogs, including a complete alanine scan and a full set of N-and C-terminal truncated analogs. The fallaxin analogs were tested for hemolytic activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant S. aureus, (VISA), methicillinsusceptible S. aureus (MSSA), E. coli, K. pneumoniae, and P. aeruginosa. We identified several analogs, which showed improved antibacterial activity compared to fallaxin. Our best candidate was FA12, which displayed MIC values of 3.12, 25, 25, and 50 mM against E. coli, K. pneumoniae, MSSA, and VISA, respectively. Furthermore, we correlated the antibacterial activity with various structural parameters such as charge, hydrophobicity AEHae, mean hydrophobic moment AEm H ae, and a-helicity. We were able to group the active and inactive analogs according to mean hydrophobicity AEHae and mean hydrophobic moment AEm H ae. Far-UV CD-spectroscopy experiments on fallaxin and several analogs in buffer, in TFE, and in membrane mimetic environments (small unilamellar vesicles) indicated that a coiled-coil conformation could be an important structural trait for antibacterial activity. This study provides data that support fallaxin analogs as promising lead structures in the development of new antibacterial agents.Keywords: alanine scan; antibacterial activity; coiled-coil conformation; fallaxin; solid-phase peptide synthesis Reprint requests to: Paul Robert Hansen, Department of Natural Sciences, Faculty of Life Sciences, University of Copenhagen, 1871 Frederiksberg C, Denmark; e-mail: prh@life.ku.dk; fax: 45-35332398.Abbreviations: ACTH, adrenocorticotropic hormone; ATCC, American type culture collection; Boc, tert-butyloxycarbonyl; BSA: bovine serum albumin; CFU, colony forming unit; CPD, citrate-phosphatedextrose; DIEA, diisopropylethylamine; DMPC, 1,2-dimyristoyl-snglycero-3-phosphocholine; DMPG, 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol; DTT: dithiothrethiol; Fmoc: 9-fluorenylmethoxy; AEHae, mean hydrophobicity; HC 50 : the toxin concentration yielding 50% lysis of a 1% suspension of erythrocytes after 45 min at 37°C; AEm H ae, mean hydrophobic moment; HATU, (2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate); HOBt, 1-hydroxybenzotriazole; MALDI-TOF MS, matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry; MIC, minimum inhibitory concentration; NMP, N-methyl-2-pyrrolidone; SUV, small unilamellar vesicles; TFA, trifluoroacetic acid; TFE, trifluoroethanol; TIS, triisopropylsilane; Trt, triphenylmethyl.Article and publication are at

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An antimicrobial peptide from the skin secretions of the mountain chicken frog Leptodactylus fallax (Anura:Leptodactylidae)

Cited by 47 publications

References 29 publications

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

Purification and Properties of Laticeptin, an Antimicrobial Peptide from Skin Secretions of the South American Frog Leptodactylus laticeps

Structure–activity study of the antibacterial peptide fallaxin

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