Advances in genomic tools such as tiling arrays, comparative Staurosporine nmr genome hybridization microarrays (array CGH), and ultra-high-throughput sequencing

are now allowing researchers to have a better understanding of the genotypic changes associated with adaptation [for review see (Dettman et al., 2012)], such as drug resistance (Selmecki et al., 2010). The applications of these tools to time-course isolates obtained in vitro and in vivo will yield the necessary correlations between genotypic and phenotypic changes in resistant strains and help researchers to gain a firmer grasp on the evolutionary trajectories of fungal pathogens during exposure HM781-36B chemical structure to antifungal agents. In addition to the aforementioned factors (e.g. population size, relative fitness coefficients, rate of beneficial mutations, etc.)

that contribute to the population dynamics during adaptive evolution, additional factors such as dosing regimens and the mode of action of the antifungal agent may also contribute to the population dynamics during the emergence of drug resistance in C. albicans. A series of in vivo studies in murine model shed some light on the importance of some of these factors on antifungal drug resistance in C. albicans (Andes et al., 2006). Andes et al. (2006) investigated the impact of different fluconazole (a fungistatic agent) dosing regimens, using different dose levels and dosing intervals, on the outgrowth of resistant strain with different initial ratios of drug-resistant and susceptible strains in a murine model; they found a lower but more frequent dosage of fluconazole led to less frequent outgrowth of the resistant strain compared with higher but more infrequent dosage. Another study by the same

group revealed a similar effect of dosing regimen on drug resistance emergence when they evolved an initially drug-susceptible strain of C. albicans in a murine model (Andes et al., 2006). Results from these studies suggest different selection strategies may have different impacts on the expansion of drug-resistant genotypes click here within the population, leading to different population dynamics and ultimately to different evolutionary outcomes. In addition, they found that if the initial population contained at least 10% of the drug-resistant clone, the evolving population behaved phenotypically as entirely drug resistant, suggesting that the population structure prior to drug exposure is an important factor in determining the evolutionary outcome of the population (Andes et al., 2006). The mode of action of the antifungal agent may also be a contributing factor on the emergence of drug resistance.