Candida albicans blastospores and hyphae respond differentially to fluconazole: additional virulence factor of germination process

Abstract

Background: The morphologic transition from yeasts (blastospores) to hyphae, through the germination process, is a crucial virulence factor of Candida albicans ( C. albicans), as it enhances adherence, tissue invasion and biofilm formation. The study aimed at comparing fluconazole susceptibility patterns of C. albicans yeast and germinated forms. Methods: Six C. albicans strains, including C. albicans ATCC 10231 and 5 clinical isolates were tested in yeast forms and germinated forms for fluconazole susceptibility using CLSI M27-A3 broth microdilution and CLSI M44-A2 disk diffusion reference methods. Results: Fluconazole minimal inhibitory concentrations (MICs) were 0.125-1 µg/ml and 0.25-4 µg/ml for yeasts and germinated forms, respectively. The sensitivities of yeasts were higher than those of their corresponding germinated forms with 1 to 4-fold dilutions differences. The MIC₅₀s of yeasts and germinated forms were 0.125 and 1 µg/ml, respectively, with 3-fold dilution difference, while MIC₉₀s were 1 and 4 µg/ml for yeasts and germinated forms, respectively, with 2-fold dilution difference. Means of inhibition zones were 31-46.7 mm and 29.3-43.7 mm for yeasts and germinated forms, respectively. The germinated forms of all tested strains had inhibition zones smaller than those of their corresponding yeast forms with 0.2-4.8 mm differences. There was significant statistical difference in sizes of inhibition zones between yeasts and germinated forms (p = 0.043). Conclusions: Yeast and hyphae of C. albicans, both in planktonic state, respond differentially to fluconazole, as the hyphae are less sensitive than their yeasts counterparts, which can be considered as a virulence factor for hyphae, which should be considered in treatment plans of candidal infections.