title: Gomesin, a peptide produced by the spider Acanthoscurria gomesiana, is a potent anticryptococcal agent that acts in synergism with fluconazole.
abstract: Gomesin is an 18-residue cysteine-rich antimicrobial peptide produced by hemocytes of the spider Acanthoscurria gomesiana. In the present study, the antifungal properties of gomesin against Cryptococcus neoformans, the etiologic agent of cryptococcosis, were evaluated. Gomesin bound to the cell surface of cryptococci, which resulted in cell death associated with membrane permeabilization. Antifungal concentrations of gomesin were not toxic for human brain cells. Supplementation of cryptococcal cultures with the peptide (1 microM) caused a decrease in capsule expression and rendered fungal cells more susceptible to killing by human brain phagocytes. The possible use of gomesin in combination with fluconazole, a standard antifungal drug, was also evaluated. In association with fluconazole, gomesin concentrations with low antimicrobial activity (0.1-1 microM) inhibited fungal growth and enhanced the antimicrobial activity of brain phagocytes. These results reveal the potential of gomesin to promote inhibition of cryptococcal growth directly or by enhancing the effectiveness of host defenses.
authors.affiliation: Departamento de Microbiologia Geral, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fabiane M
authors.initials: FM
authors.lastname: Barbosa
authors.forename: Sirlei
authors.initials: S
authors.lastname: Daffre
authors.forename: Rosa A
authors.initials: RA
authors.lastname: Maldonado
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development; D004347:Drug Interactions; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D010586:Phagocytes / Q000187:drug effects; D013112:Spiders / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; C415987:gomesin; D015725:Fluconazole