title: Activity of Scorpion Venom-Derived Antifungal Peptides against Planktonic Cells ofCandidaspp. andCryptococcus neoformansandCandida albicansBiofilms.
abstract: The incidence of fungal infections has been increasing in the last decades, while the number of available antifungal classes remains the same. The natural and acquired resistance of some fungal species to available therapies, associated with the high toxicity of these drugs on the present scenario and makes an imperative of the search for new, more efficient and less toxic therapeutic choices. Antimicrobial peptides (AMPs) are a potential class of antimicrobial drugs consisting of evolutionarily conserved multifunctional molecules with both microbicidal and immunomodulatory properties being part of the innate immune response of diverse organisms. In this study, we evaluated 11 scorpion-venom derived non-disulfide-bridged peptides againstCryptococcus neoformansandCandidaspp., which are important human pathogens. Seven of them, including two novel molecules, showed activity against both genera with minimum inhibitory concentration values ranging from 3.12 to 200 μM and an analogous activity againstCandida albicansbiofilms. Most of the peptides presented low hemolytic and cytotoxic activity against mammalian cells. Modifications in the primary peptide sequence, as revealed byin silicoand circular dichroism analyses of the most promising peptides, underscored the importance of cationicity for their antimicrobial activity as well as the amphipathicity of these molecules and their tendency to form alpha helices. This is the first report of scorpion-derived AMPs againstC. neoformansand our results underline the potential of scorpion venom as a source of antimicrobials. Further characterization of their mechanism of action, followed by molecular optimization to decrease their cytotoxicity and increase antimicrobial activity, is needed to fully clarify their real potential as antifungals.
authors.affiliation: Laboratory of Molecular Biology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Guilhelmelli
authors.affiliation: Laboratory of Molecular Biology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Nathália
authors.initials: N
authors.lastname: Vilela
authors.affiliation: Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Karina S
authors.initials: KS
authors.lastname: Smidt
authors.affiliation: Laboratory of Molecular Biology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Marco A
authors.initials: MA
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Molecular Biophysics, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Alice
authors.initials: A
authors.lastname: da Cunha Morales Álvares
authors.affiliation: Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Maria C L
authors.initials: MC
authors.lastname: Rigonatto
authors.affiliation: Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Pedro H
authors.initials: PH
authors.lastname: da Silva Costa
authors.affiliation: Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Aldo H
authors.initials: AH
authors.lastname: Tavares
authors.affiliation: Laboratory of Molecular Biophysics, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Sônia M
authors.initials: SM
authors.lastname: de Freitas
authors.affiliation: Faculty of Medicine, University of Brasília Brasília, Brazil.
authors.forename: André M
authors.initials: AM
authors.lastname: Nicola
authors.affiliation: Center of Proteomic and Biochemistry Analysis, Post Graduation in Biotechnology and Genomic Sciences, Catholic University of Brasília Brasília, Brazil.
authors.forename: Octávio L
authors.initials: OL
authors.lastname: Franco
authors.affiliation: Laboratory of Molecular Biology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Lorena da Silveira
authors.initials: LD
authors.lastname: Derengowski
authors.affiliation: Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Elisabeth F
authors.initials: EF
authors.lastname: Schwartz
authors.affiliation: Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Márcia R
authors.initials: MR
authors.lastname: Mortari
authors.affiliation: Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Anamélia L
authors.initials: AL
authors.lastname: Bocca
authors.affiliation: Laboratory of Molecular Biology, Department of Cellular Biology, Institute of Biological Sciences, University of BrasíliaBrasília, Brazil; Faculty of Ceilândia, University of BrasíliaBrasília, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Albuquerque
authors.affiliation: Laboratory of Molecular Biology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília Brasília, Brazil.
authors.forename: Ildinete
authors.initials: I
authors.lastname: Silva-Pereira
keywords: Candida albicans; Candida spp.; Cryptococcus neoformans; antifungal drugs; antimicrobial peptides; scorpions venom