Host association induces genome changes in Candida albicans which alters its virulence

Candida albicansis an opportunistic fungal pathogen of humans that is typically diploid yet, has a highly labile genome that is tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial forC. albicansto adapt to changing or stress environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, which includes mating between diploids or stress-induced mitotic defects to produce tetraploids and non-meiotic ploidy reduction. However, it remains largely unknown how genetic background contributes toC. albicansgenome instabilityin vitroorin vivo.Here, we tested how genetic background, ploidy and host environment impactC. albicansgenome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied acrossC. albicansstrains. We also assessed whether host-induced genomic changes resulted in any consequences on growth rate and virulence phenotypes and found that many host derived isolates had significant changes compared to their parental strains. Interestingly, host derivatives from diploidC. albicanspredominantly displayed increased virulence, whereas host derivatives from tetraploidC. albicanshad mostly reduced virulence. Together, these results are important for understanding how host-induced genomic changes inC. albicansalter the relationship between the host andC. albicans.