Candida albicans is a commensal yeast found naturally in the human G.I. tract that can cause lethal infections, especially in immune compromised patients. Azoles, the most common class of drugs used to treat candidemia and candidiasis, target the enzyme 14a-demethylase. By doing so they inhibit production of ergosterol, an essential component of the cell membrane. Resistance to azoles is often seen in patients who had prior drug exposure and in some clinical isolates, resistance has appeared very rapidly, motivating the study of how resistance (mutations resulting in heritable changes) and tolerance (alterations providing the ability to survive in the presence of the drug) arise.
In this project, we studied the effects of fluconazole on a broad range of C. albicans isolates spanning the 4 major MLST-identified clades. All but one strain had very similar MICs initially. Following exposure to low or high fluconazole levels for 24h, all strains exhibited increased sensitivity to the drug. High levels of fluconazole were more efficacious than low levels of the drug, and cells grown in nutrient-poor media were more sensitive to a second exposure to FLC than cells grown in rich media. No difference in MIC was detectable with liquid CLSI assays; disk diffusion assays revealed reduced tolerance after drug exposure. Strain recovery from initial exposure to fluconazole was also studied. In summary, most strains do not undergo a rapid changes in fluconazole MIC following short times of drug exposure, but the degree of drug tolerance changes significantly.
