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Sci Rep ; 10(1): 10327, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32587287

RESUMO

Candida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis. Fungal infections treatment faces three major challenges: the limited number of therapeutic options, the toxicity of the available drugs, and the rise of antifungal resistance. In this study, we demonstrate the antifungal activity and mechanism of action of peptides ToAP2 and NDBP-5.7 against planktonic cells and biofilms of C. albicans. Both peptides were active against C. albicans cells; however, ToAP2 was more active and produced more pronounced effects on fungal cells. Both peptides affected C. albicans membrane permeability and produced changes in fungal cell morphology, such as deformations in the cell wall and disruption of ultracellular organization. Both peptides showed synergism with amphotericin B, while ToAP2 also presents a synergic effect with fluconazole. Besides, ToAP2 (6.25 µM.) was able to inhibit filamentation after 24 h of treatment and was active against both the early phase and mature biofilms of C. albicans. Finally, ToAP2 was protective in a Galleria mellonella model of infection. Altogether these results point to the therapeutic potential of ToAP2 and other antimicrobial peptides in the development of new therapies for C. albicans infections.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Animais , Antifúngicos/uso terapêutico , Candidíase/microbiologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Modelos Animais de Doenças , Farmacorresistência Fúngica , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Mariposas , Proteínas Citotóxicas Formadoras de Poros/uso terapêutico
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