Abstract

Cryptococcus gattii is an etiologic agent of cryptococcosis and a serious disease that affects immunocompromised and immunocompetent patients worldwide. The therapeutic arsenal used to treat cryptococcosis is limited to a few antifungal agents, and the ability of C. gattii to form biofilms may hinder treatment and decrease its susceptibility to antifungal agents. The objective of this study was to evaluate the antifungal and antibiofilm activities of an ethanolic extract of Cochlospermum regium (Schrank) Pilger leaves against C. gattii. The antifungal activity was assessed by measuring the minimum inhibitory concentration (MIC) using the broth microdilution technique and interaction of the extract with fluconazole was performed of checkerboard assay. The antibiofilm activity of the extract was evaluated in 96-well polystyrene microplates, and the biofilms were quantified by counting colony forming units. The extract showed antifungal activity at concentrations of 62.5 to 250 μg/mL and when the extract was evaluated in combination with fluconazole, C. gattii was inhibited at sub-MIC levels. The antibiofilm activity of the extract against C. gattii was observed both during biofilm formation and on an already established biofilm. The results showed that the ethanolic extract of the leaves of C. regium shows promise for the development of antifungal drugs to treat cryptococcosis and to combat C. gattii biofilms.

Highlights

  • Cryptococcosis is a fungal infection that occurs worldwide

  • All strains were inhibited by ECR, with minimum inhibitory concentration (MIC) ranging from 62.5 to 250 μg/mL

  • When ECR was evaluated in combination with fluconazole, C. gattii was inhibited at sub-MIC levels

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Summary

Introduction

Despite the predominant result of opportunistic infections of immunocompromised patients, the incidence of infections among immunocompetent individuals is increasing [1,2,3,4]. Despite the importance of this disease, the treatment of cryptococcosis is limited to the antifungals fluconazole and amphotericin B, which are used alone or in combination with 5-flucytosine [7]. The primary etiological agents of cryptococcosis are species of the complexes Cryptococcus neoformans and C. gattii [8], which respond differently to the treatment established for meningoencephalitis [9]. Species of the C. gattii complex can compromise immunocompetent individuals and cause severe diseases of the central nervous system, such as meningitis, encephalitis, and meningoencephalitis [9].

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