Predicting the emergence of resistance to antifungal drugs.

The emergence of antifungal drug resistance is inevitable. Here I discuss antibiotic resistance in the context of the adaptive potential of fungi and I propose an approach to predicting the evolution of antifungal resistance using experimental evolution of DNA sequences and microbial populations. Prediction is based on determination of evolutionary potential at two levels, the gene and the genome. At the level of the gene, evolutionary potential depends on the sequence space of candidate resistance genes defined by the fitness effects of all possible mutations in all possible combinations. At the level of the genome, evolutionary potential depends on the adaptive landscape defined by the fitness effects of all possible interactions among alleles constituting the genotype.