Clade Related Induction of Fluconazole Resistance among Candida albicans Isolates

Objective: Candida albicans is the causative agent of oropharyngeal candidiasis (OPC), the most common oral complication in HIV/AIDS patients. Antifungal resistance among C. albicans isolates from HIV/AIDS patients has been frequently reported. Five distinct genetic clades of C. albicans have been established, including a clade related antifungal resistance to amphotericin B and 5-flucytocine. The purpose of this study was to determine whether there is a clade related difference in the in vitro induction of fluconazole resistance in C. albicans. Methods: Eight C. albicans isolates were selected from each of the previously fingerprinted clades (I, II, III, SA, and NG). Resistance was induced through serial growth in increasing concentrations of fluconazole. The stability of the acquired resistance was determined through serial passage in fresh medium and plating on 64µg/ml fluconazole agar plates. Resistance was regarded to be stable if growth was still observed after the sixth passage to fresh medium. Results: Fluconazole resistance could be induced in 6 isolates of each of clades I, SA and NG, in all 8 isolates of clade III and in 7 isolates of clade II. Seven isolates from clade III readily acquired resistance while all the isolates from clade NG had to be repeatedly incubated. Only 2 isolates from clade SA readily acquired resistance, while the other 6 had to be repeatedly incubated. Clade I, II and SA each had 2 isolates that retained the acquired resistance, while clade III, despite having readily acquired the resistance, had only 1 isolate that remained resistant. Clade NG had no isolates that retained their induced resistance. Conclusion: No clade related acquisition of fluconazole resistance was demonstrated although it was observed that certain strains can readily acquire resistance to fluconazole. A minority of isolates retained the in vitro acquired resistance.