Grant: Project Grant - PA: Infection and Immunity (Early Career Research Support)

Fungal pathogens are critical threats to global health, affecting 1 in 50 Canadians, and over 300 million people across the world, annually. Fungal infections are highly prevalent among immunocompromised individuals (e.g., HIV/AIDS patients, cancer patients, elderly) but also impact healthy individuals, and demonstrate substantial levels of co-infection with other pathogens (e.g., COVID-19). If left untreated or in the absence of effective treatment options, mortality rates reach as high as 90%. The treatment of fungal infections is challenging due to a limited repertoire of antifungal drugs, and the emergence and evolution of antifungal resistance. Such resistance can develop through prolonged antifungal treatment regimes, the widespread use of antifungals in medicine and agriculture, climate change and international travel that introduce pathogens to new environments, and the occurrence of cross-species mating between fungi. Therefore, new strategies to overcome or reverse resistance are urgently needed. In this proposal, we use a combination of biological and computational strategies to investigate fluconazole resistance in the human fungal pathogen, Cryptococcus neoformans, to provide an in-depth understanding of mechanisms conferring resistance, and to propose novel strategies to overcome resistance and make our existing antifungals effective against cryptococcal infection once again.