Genomic Plasticity of the Human Fungal Pathogen Candida albicans

Abstract

The genomic plasticity of Candida albicans, a commensal and common opportunistic fungal pathogen, continues to reveal unexpected surprises. Once thought to be asexual, we now know that the organism can generate genetic diversity through several mechanisms, including mating between cells of the opposite or of the same mating type and by a parasexual reduction in chromosome number that can be accompanied by recombination events (2, 12, 14, 53, 77, 115). In addition, dramatic genome changes can appear quite rapidly in mitotic cells propagated in vitro as well as in vivo. The detection of aneuploidy in other fungal pathogens isolated directly from patients (145) and from environmental samples (71) suggests that variations in chromosome organization and copy number are a common mechanism used by pathogenic fungi to rapidly generate diversity in response to stressful growth conditions, including, but not limited to, antifungal drug exposure. Since cancer cells often become polyploid and/or aneuploid, some of the lessons learned from studies of genome plasticity in C. albicans may provide important insights into how these processes occur in higher-eukaryotic cells exposed to stresses such as anticancer drugs.

Adaptive mechanisms in pathogens: universal aneuploidy in Leishmania

“…In C. albicans, aneuploidy can give an adaptive advantage in stressful conditions after only one or two cell divisions, and the original euploid state can be restored in one step when conditions are returned to normal [54]. Reversion to the normal state is also observed in L. infantum, where additional chromosomes disappeared after removal of drug pressure [11].…”

“…Alternatively, if a tri-or tetrasomic state is stable for a longer evolutionary period during which recombination occurs between the homologous chromosomes, this could provide a selective advantage from a greater net chromosome length on which mutations can occur while still keeping the original gene copies [54]. In this scenario, reversion to disomy could cause perceived higher heterozygosity depending on the chromosomes lost and would also violate assumptions of a neutral molecular clock [70].…”

“…The common fungal pathogen Candida albicans displays a high level of genomic plasticity, including aneuploidy, affecting one to three of the eight chromosomes, depending on the strain [54]. This is apparently beneficial under selective pressure: for example, aneuploid C. albicans strains under drug pressure have an increased fitness [55].…”

“…Genomic changes in aneuploidy-tolerating pathogens can occur at a rapid rate [54,59,60]. In C. albicans, aneuploidy can give an adaptive advantage in stressful conditions after only one or two cell divisions, and the original euploid state can be restored in one step when conditions are returned to normal [54].…”

The RNA-Binding Protein Whi3 Is a Key Regulator of Developmental Signaling and Ploidy inSaccharomyces cerevisiae

“…However, no functional studies have been performed with Whi3 homologs in these organisms and it remains to be determined whether these putative RNAbinding proteins fulfill orthologous functions. It will be especially interesting to see whether Whi3 homologs are also involved in the regulation of ploidy in these fungi, given the fact that C. albicans has been found to perform rapid changes in genome content during mitosis and that variable chromosome organization is thought to be a commonly used mechanism of pathogenic fungi for the adaptation to changing growth conditions (Selmecki et al 2010). Figure 8 Wiring diagram for Whi3 regulation of cell size, stability of ploidy, biofilm formation, and stress response.…”