Ploidy changes in human fungal pathogens: Going beyond sexual reproduction

Two major genetic clusters (A and B) of C. glabrata isolates were identified through multilocus sequence typing (MLST), with most isolates from China belonging to cluster A, whereas the majority of isolates from other countries belonged to cluster B. C. glabrata isolates from both genetic clusters were able to undergo ploidy changes, although isolates from cluster A demonstrated a greater haploid-to-higher-ploidy switching frequency than those from cluster B. Given the close phylogenetic relationship between C. glabrata and S. cerevisiae, a similar mechanism of endoreduplication could be involved in both species, as spontaneous diploidization events are relatively common in the latter [25]. Aneuploid and non-baseline ploidy states are often unstable and can give rise to additional genetic variants. https://doi.org/10.1371/journal.ppat.1010954.g001 Polyploid titan cells in C. neoformans The pathogenic basidiomycete Cryptococcus neoformans ubiquitously exists in the environment, including in the soil, on trees, and in bird droppings. Interestingly, some clinical isolates of C. auris can form enlarged clusters of cells due to the failure of cell division to release daughter cells, and these may increase survival by mechanisms similar to those favoring C. neoformans titan cells. Studies in C. neoformans have linked ploidy increases to cell cycle regulation; one study revealed that suppression of the cell cycle regulator Cln1 can enable re-replication of DNA producing polyploid titan cells [31], while a related study showed a role for cyclins and cyclin-dependent kinases in regulating endoreplication [32].