Experimental evolution of drug resistance in human fungal pathogens.

Experimental evolution in vitro is a powerful tool to uncover the factors that contribute to resistance evolution and understand the genetic basis of adaptation. Here, we discuss recent experimental evolution studies from human fungal pathogens. We synthesize the results to highlight the common threads that influence resistance acquisition. The picture that emerges is that drug resistance consistently appears readily and rapidly. Mutations are often found in an overlapping set of genes and genetic pathways known to be involved in drug resistance, including whole or partial chromosomal aneuploidy. The likelihood of acquiring resistance and cross-resistance between drugs seems to be influenced by the specific drug (not just drug class), level of drug, and strain genetic background. We discuss open questions, such as the potential for increases in drug tolerance to evolve in static drugs. We highlight opportunities to use this framework to probe how different factors influence the rate and nature of adaptation to antifungal drugs in fungal microbes through a call for increased reporting on all replicates that were evolved, not just those that acquired resistance.