Ploidy variation as an adaptive mechanism in human pathogenic fungi

Carl A. Morrow, James A. Fraser

Changes in ploidy have a profound and usually negative influence on cellular viability and proliferation, yet the vast majority of cancers and tumours exhibit an aneuploid karyotype. Whether this genomic plasticity is a cause or consequence of malignant transformation remains uncertain. Systemic fungal pathogens regularly develop aneuploidies in a similar manner during human infection, often far in excess of the natural rate of chromosome nondisjunction. As both processes fundamentally represent cells evolving under selective pressures, this suggests that changes in chromosome number may be a concerted mechanism to adapt to the hostile host environment. Here, we examine the mechanisms by which aneuploidy and polyploidy are generated in the fungal pathogens Candida albicans and Cryptococcus neoformans and investigate whether these represent an adaptive strategy under severe stress through the rapid generation of large-scale mutations. Insights into fungal ploidy changes, strategies for tolerating aneuploidies and proliferation during infection may yield novel targets for both antifungal and anticancer therapies.