Divergence in Fitness and Evolution of Drug Resistance in Experimental Populations of Candida albicans

Population genomics of drug resistance in Candida albicans

“…Populations D8, D9, D11, and D12 were four of six populations that were evolved in the presence of twice their most recently measured MIC of fluconazole (Roerig-Pfizer, New York). These populations were selected for genome-wide expression profiling because they represented the diversity of adaptive trajectories, MICs, fitness profiles, and expression patterns of four genes known to be involved in azole resistance (10,11). All of the populations included in this study were profiled at generation 330, the end of the evolution experiment.…”

“…RNA was prepared using glass beads (22) and Northern blots were prepared according to a standard protocol (23). The following primers were used for amplification of the ten probes from genomic DNA of the ancestor of the experimental populations: ADH4, 5Ј-ACATTTGGGTGGAGAAACAG-3Ј and *In a previous study (11), fitness was measured relative to the genetically marked ancestor as the difference in the number of doublings of the two competitors (evolved population sample minus ancestor), standardized by the total number of doublings in the competition assay. Fitness measurements are the average from three replicates Ϯ 95% confidence intervals.…”

“…The populations evolved with the drug diverged in their adaptive trajectories, reaching different levels of drug resistance associated with distinct molecular mechanisms of resistance (10) and with distinct fitness characteristics (11). In the present study, we measured changes in genome-wide gene expression in these evolved populations relative to their common ancestor by using DNA microarrays.…”

“…We therefore profiled populations grown in a uniform environment without the drug. We sampled populations for transcriptional profiling (Table 1) to encompass the range of minimum inhibitory concentrations (MICs) of fluconazole, expression patterns of four genes involved in azole resistance, and fitness (10,11). We measured gene expression profiles of four populations that evolved with the drug for 330 generations.…”

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

“…The lowest concentration of a drug that inhibits growth, generally by either 50% or 90%, is defined as the MIC. Although MIC assays provide a measure of how the pathogen will respond to drug treatment, they are not always accurate predictors of the response in vivo or even of how the resistant pathogen will compete against a drug-sensitive counterpart in vitro (110,114). MIC assays do not account for how pharmacokinetics, host-pathogen interactions, microbial interactions, and environmental factors affect drug resistance and clinical outcomes.…”