Audrey Hilk

Candida albicans is an opportunistic human fungal pathogen with the potential to cause severe disease in immunocompromised individuals. The genome of C. albicans is highly plastic and a wide variety of large genome changes occur. These genome changes include aneuploidy, segmental aneuploidy, polyploidy, and loss of heterozygosity. Specifically, copy number variation (CNV) and loss of heterozygosity (LOH) are often observed in drug-resistant Candida albicans due to the amplification of genes associated with drug resistance. The frequency by which large genome changes occur is increased during exposure to stressful conditions including oxidative stress and antifungal drugs. C. albicans is exposed to oxidative stress during infections, as innate immune cells produce hydrogen peroxide and superoxide in defense against microbial organisms. However, the mechanisms behind adaptation to oxidative stress and antifungal drug resistance are not well understood. To determine the impact of oxidative stress on the rate and dynamics of large genome changes, we performed an in vitro evolution experiment in the presence and absence of oxidative stress over 5 days. For this experiment, we engineered C. albicans strains with fluorescent markers on multiple chromosomes. These strains enabled us to quantify large genome changes (loss and gain events) that occurred in individual cells within populations using flow cytometry. Here, we demonstrate the frequency of large genome changes within populations that have undergone adaptation to oxidative stress and the subsequent effects of these genome changes on phenotype.