Genome and population dynamics in pathogenic yeasts

Rapid responses to acute stresses are essential for stress survival and adaptation. An excellent microbial model for this process is the rapid emergence of drug responses in fungal pathogens. Fungi can adapt and survive drug concentrations that inhibit the growth of progenitor cells. They often do so via large effect size mutations involving whole chromosomes, chromosome arms as well as some point mutations, in a manner similar to cancer cells responding to chemotherapy drugs. Specifically, they undergo ploidy switches, alter chromosome copy number (become aneuploid) and undergo frequent loss of heterozygosity, via recombination and chromosome mis-segregation. In addition, fungi can respond with increased cell to cell variability in their response to drugs with small or large populations of cells acquiring the ability to grow in drug concentrations that inhibit others. This property has been ignored clinically but is likely to be an important factor in how well infections respond to antifungal therapies. Overall, fungi exhibit a broad repertoire of different mechanisms that enable rapid and transient generation of genomic diversity, upon which the strong selective pressure of antifungal drugs can act to facilitate improved survival and growth of the fungal pathogen during antifungal therapy.