title: Anti-fungal activity of Ctn[15-34], the C-terminal peptide fragment of crotalicidin, a rattlesnake venom gland cathelicidin.
abstract: Crotalicidin (Ctn), a 34-residue cathelicidin from a South American rattlesnake, and its fragment (Ctn[15-34]) have shown anti-infective and cytotoxic activities against Gram-negative bacteria and certain tumor lines, respectively. The extent of such effects has been related to physicochemical characteristics such as helicity and hydrophobicity. We now report the anti-fungal activity of Ctn and its fragments (Ctn[1-14]) and (Ctn[15-34]). MIC determination and luminescent cell viability assays were used to evaluate the anti-infective activity of Ctn and its fragments (Ctn[1-14]) and (Ctn[15-34]) as anti-fungal agents against opportunistic yeast and dermatophytes. Cytotoxicity towards healthy eukaryotic cells was assessed in vitro with healthy human kidney-2 (HK-2) cells and erythrocytes. The checkerboard technique was performed to estimate the effects of combining either one of the peptides with amphotericin B. Ctn was the most active peptide against dermatophytes and also the most toxic to healthy eukaryotic cells. Fragments Ctn[1-14] and Ctn[15-35] lost activity against dermatophytes, but became more active against pathogenic yeasts, including several Candida species, both clinical isolates and standard strains, with MICs as low as 5 μm. Interestingly, the two peptide fragments were less cytotoxic to healthy HK-2 cells and less hemolytic to human erythrocytes than the standard-of-care amphotericin B. Also noteworthy was the synergy between Ctn peptides and amphotericin B, with consequent reduction in MICs of both drug and peptides. Altogether, Ctn and its fragments, particularly Ctn[15-34], are promising leads, either alone or in combined regimen with amphotericin B, for the treatment of fungal diseases.
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Ceará, Brazil.|Laboratory of Biochemistry and Biotechnology, Institute for Marine Sciences, Federal University of Ceará, Ceará, Brazil.|Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.
authors.forename: Carolina Sidrim P
authors.initials: CS
authors.lastname: Cavalcante
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Ceará, Brazil.|Laboratory of Biochemistry and Biotechnology, Institute for Marine Sciences, Federal University of Ceará, Ceará, Brazil.
authors.forename: Cláudio B
authors.initials: CB
authors.lastname: Falcão
authors.affiliation: Center of the Agricultural Sciences and Biological, Acaraú Valley State University, Ceará, Brazil.
authors.forename: Raquel Os
authors.initials: RO
authors.lastname: Fontenelle
authors.affiliation: Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Andreu
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Ceará, Brazil.|Laboratory of Biochemistry and Biotechnology, Institute for Marine Sciences, Federal University of Ceará, Ceará, Brazil.
authors.forename: Gandhi
authors.initials: G
authors.lastname: Rádis-Baptista
mesh_terms: D000595:Amino Acid Sequence; D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003435:Crotalid Venoms / Q000737:chemistry*; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D015003:Yeasts / Q000187:drug effects; D054804:Cathelicidins
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D003435:Crotalid Venoms; D010446:Peptide Fragments; C000618137:crotalicidin; D000666:Amphotericin B; D054804:Cathelicidins