Developmental Projects

DP004 Wong

An outbreak of serious infections caused by the emerging fungus Cryptococcus gattii was recognized on Vancouver Island, British Columbia in 2002, and this epidemic has since spread to mainland Canada, Washington and Oregon.  C. gattii difers from related fungi in that it (i) infects immunologically normal people and (ii) responds poorly to conventional antifungal therapy.  We found in preliminary studies that C. gattii strains from the Pacific Northwest were significantly more resistant to multiple azole antifungal drugs than were C. gattii strains from other geographic areas or than the more common fungal pathogen Cryptococcus neoformans.  Therefore, this project will examine whether known causes of azole resistance in other fungi are also responsible for azole resistance in C. gattii.  We will (i) compare drug-susceptible and drug-resistant fungal strains for their abilities to pump azole antifungal drugs out of the cell, (ii) measure the amounts of a key enzyme target of azole antifungals drug that drug-susceptible and drug-resistant fungi produce, and (iii) test multiple antifungal drugs for their abilities to inhibit the enzymes derived from drug-susceptible and drug-resistant C. gattii strains.  Understanding why C. gattii becomes resistant to azoles may lead to improved methods for treating this important and emerging infectious disease.