Evaluation of caspofungin effects in agents of chromoblastomycosis

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Abstract

Chromoblastomycosis is a chronic disease that affects cutaneous and subcutaneous tissues and is caused by fungi of the Herpotrichiellaceae family. It is considered a tropical neglected disease by the World Health Organization. The disease is considered a therapeutic challenge due to low cure rates and frequent cases of relapse. The treatment is based on the use of antifungals, mainly itraconazole. Among the most recent antifungal options is the echinocandin class, which acts by inhibiting the production of β-glucans in the fungal cell wall. The aim of this study was to evaluate the effects of the caspofungin treatment in two species of Fonsecaea, agents of chromoblastomycosis and identify a possible therapeutic option. For the work, it was used Fonsecaea pedrosoi and Fonsecaea monophora, to determine the minimum effective concentrations (MEC) of Caspofungin by microdilution method and use of the vital dye Resazurin. The minimum fungicidal concentration (MFC) was also established. Effect of caspofungin on spores’ germination, fungal morphology and in cell wall composition were analyzed. Strains had similar MEC of 4-8μg/mL. The effect on metabolism was dose-dependent, F. monophora presented reduction of metabolism from dose of 2 μg/mL, while 8μg/mL promoted metabolism alteration on F. pedrosoi. For both strains, caspofungin was fungistatic. After exposure to the drug, even in high doses, fungal growth was detected in a drug-free environment. Caspofungin treatment for 24 and 48h reduced conidia germination, with short, irregular and more branched hyphae. The presence of caspofungin 8μg/mL induced an increased exposure of β-glucans in F. pedrosoi. The exposition to caspofungin affects fungal morphology and promotes alteration in the cell wall composition. The echinocandin effects on Fonsecaea spp should be evaluated in a more detailed way to explore its modulatory effect on the immune response, by inducing changes in the structure of the fungal cell wall, as demonstrated for other fungal pathogens, and considered to be used in a combined therapy.

Institutions
  • 1 Universidade de Brasília
Track
  • Clinical Microbiology
Keywords
CHROMOBLASTOMYCOSIS
Echinocandins
Caspofungin
FONSECAEA
β-glucan