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Prospection of secondary metabolites of Actinomycetes with inhibitory activity against clinical and environmental pathogenic fungi

Abstract

Antifungal resistance is a growing threat to public health, with a drastic reduction in the effectiveness of classic antifungals, such as azoles. Thousands of people die annually as a consequence of fungal infections associated with the long-term use of broad-spectrum antibiotics, immunosuppressive therapies, ICU admissions, extensive burns, major surgery, malignancy and, currently, the COVID-19 pandemic. Yeasts of Candida and Cryptococcus genus and filamentous fungi such as Aspergillus species and dematiaceous fungi are relevant causal agents. The limited antifungal therapeutic arsenal available, and the detection of naturally resistant species or carriers of mutations that confer resistance, indicate the urgent need for new therapeutic alternatives. The wealth of Brazilian biodiversity is a potential for drug development. The known antimicrobial potential of metabolites produced by actinomycetes and the availability of these isolates at CBMAI-Unicamp, led to the proposal to investigate the chemical potential of these species for evaluation against fungal isolates, kept in the collections CBMAI and LIF in search of new antifungal compounds. Microbial extracts will be produced, which activity will be evaluated against the first isolates of Aspergillus fumigatus carrying resistance mutations reported in Brazil (Collection LIF-FCM-UNICAMP), a variety of dematiaceous fungi (CBMAI) and yeasts and filamentous fungi isolated from patients in HC-UNICAMP. Antagonism and disk diffusion tests will be performed to screen the most promising crude extracts, followed by broth microdilution of the crude extracts to select those that will then be subjected to detailed chemical analysis, and fractionation to determine the active principle. All isolates will be identified using a polyphasic approach, preserved by long-term methods and associated information made available in the CBMAI and LIF catalogs. (AU)

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