Divergence in fitness and evolution of drug resistance in experimental populations of Candida albicans

The dissemination and persistence of drug-resistant organisms in nature dep ends on the relative fitness of sensitive and resistant genotypes, While re sistant genotypes are expected to be at an advantage compared to less resis tant genotypes in the presence of drug, resistance mag incur a cost; resist ant genotypes may be at a disadvantage in the absence of drug. We measured the fitness of replicate experimental populations of the pathogenic yeast C andida albicans founded from a single progenitor cell in a previous study ( L, E, Cowen, D, Sanglard, D, Calabrese, C, Sirjusingh, J.B. Anderson, and L . hi. Kohn, J, Bacteriol, 182:1515-1522, 2000) and evolved in the presence, and in the absence, of the antifungal agent fluconazole. Fitness was measu red both in the presence and in the absence of fluconazole by placing each evolved population in direct competition with the drug-sensitive ancestor a nd measuring the reproductive output of each competitor in the mixture. Pop ulations evolved in the presence of drug diverged in fitness, Any significa nt cost of resistance, indicated by reduced fitness in the absence of drug, was eliminated with further evolution. Populations evolved in the absence of drug showed more uniform increases in fitness under both conditions. Fit ness in the competition assays was not predicted by measurements of the MIC s, doubling times, or stationary-phase cell densities of the competitors in isolation, suggesting the importance of interactions between mixed genotyp es in competitions.