In Vitro Fluconazole Exposure Promotes Switch Phenotypes With Altered Virulence Traits in the Pathogenic Yeast Candida Tropicalis

Abstract

Candida tropicalis is an opportunistic yeast pathogen that has the ability to develop resistance to fluconazole. This study evaluated the effect of fluconazole on the rise of phenotypic switching in C. tropicalis, an event that affects virulence in this species. C. tropicalis clinical isolate 49.07 switched reversibly at high frequency (10⁻¹ to 10⁻²) after growth in presence of subinhibitory concentration of fluconazole (0.0625 µg/mL). Phenotypic switching resulted in colonies exhibiting Star and Micro morphologies. A decrease in sensitivity to fluconazole for the Star morphotype was observed. Colonies of both switched morphotypes were associated with higher percentages of filamentous growth relative to the Smooth morphotype (clinical isolate pattern). Under filament-inducing conditions, filamentation was increased for the Star morphotype. The Star and Micro phenotypes exhibited reduced biofilm compared to the Smooth morphotype. The expression of transcription factors (EFG1 and WOR1) was increased in the Micro morphotype compared to the Smooth colonies. Our findings indicate that in vitro exposure of C. tropicalis to fluconazole may promote phenotypic switching and the occurrence of switched morphotypes with altered virulence traits.