Date of Award

5-2023

Document Type

Thesis

Department

Biochemistry

Abstract

Cryptococcus neoformans is a fungus that primarily infects humans who have weakened immune systems. An azole drug, Fluconazole, is commonly administered against C. neoformans in regions were cryptococcosis is most prevalent, most notably Sub-Saharan Africa. However, C. neoformans can gain resistance to Fluconazole through becoming an aneuploid. To better understand the basis of resistance, we employed a disk diffusion assay and investigated several chemically-distinct azole compounds with anticryptococcal properties for their effectiveness against C. neoformans and to identify potential differences in the capacity of the fungus to become resistant to each of the tested compounds. Different C. neoformans strains were tested, including both mating types. We found that Isavuconazole, Voriconazole, Difenoconazole, and Efinaconazole were superior to Fluconazole in preventing the occurrence of resistance, whereas Ketoconazole, and Myclobutanil demonstrated a relatively higher incidence of resistance. Our study has also demonstrated that the antifungal drugs differ significantly in their stability when added to the semi-solid rich growth media, which may partly explain differences in the occurrence of antifungal resistance.

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