Synergistic effect of pedalitin and amphotericin B against Cryptococcus neoformans by in vitro and in vivo evaluation

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Sangalli-Leite, Fernanda ; Scorzoni, Liliana ; Alves de Paula e Silva, Ana Carolina ; da Silva, Julhiany de Fatima ; de Oliveira, Haroldo Cesar ; Singulani, Junya de Lacorte ; Gullo, Fernanda Patricia ; da Silva, Rosangela Moraes ; Regasini, Luis Octavio ; Siqueira da Silva, Dulce Helena ; Bolzani, Vanderlan da Silva ; Fusco-Almeida, Ana Marisa ; Soares Mendes-Giannini, Maria Jose

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS; v. 48, n. 5, p. 504-511, NOV 2016.
• Web of Science Citations: 9

Abstract

Cryptococcosis is an opportunistic fungal infection responsible for high morbidity and mortality in immunocompromised patients. Combination of antifungal substances is a promising way to increase the percentage of successful treatment. Pedalitin (PED) is a natural substance obtained from Pterogyne nitens. The aim of this study was to verify the efficacy of PED alone and in combination with amphotericin B (AmB) in vitro and in vivo against Cryptococcus spp. In the in vitro assay, minimum inhibitory concentrations (MICs) of 0.125 mg/L for AmB and 3.9 mg/L for PED were found when the substances were tested alone, whilst in the combination treatment the active concentration of both decreased, with MICs of 0.03 mg/L for AmB and 1 mg/L for PED. In the survival assay, fungal burden study and histopathological assays it was possible to study the efficacy of the substances alone and in combination. The efficacy of combination therapy was considered better than monotherapy as evaluated in a Galleria mellonella model and amurine model. Thus, the combination of PED and AmB is an interesting alternative for anticryptococcal fungal treatment. Moreover, a correlation was observed between the invertebrate and murine models for this antifungal treatment combination. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. (AU)

• FAPESP's process: 15/03700-9 - Alternative animal as a model to study Paracoccidioides- host interaction: virulence, efficacy and toxicology of antifungal compounds and new preventive treatments
• Grantee: Maria José Soares Mendes Giannini
• Support type: Regular Research Grants
• FAPESP's process: 14/10446-9 - Evaluation of new therapies and biomarkers in paracoccidioidomycosis: antifungal activity of alkyl gallates in alternative models and mice and identification of circulating microRNAs
• Grantee: Junya de Lacorte Singulani
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/14023-8 - Use of peptides with anti-adhesive activity in Paracoccidoides spp. in the treatment and prophylaxis of the paracoccidioidomycosis
• Grantee: Haroldo Cesar de Oliveira
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/10917-9 - Alternative animal models: Virulence of different phylogenetic species of Paracoccidioides and effect of the 30kDa 43kDa protein and their antibodies
• Grantee: Liliana Scorzoni
• Support type: Scholarships in Brazil - Post-Doctorate