Candida tropicalis morphotypes show altered cellular structure and gene expression pre- and post-exposure to fluconazole

Abstract

A feature of Candida tropicalis is its ability to undergo phenotypic switching that can affect antifungal sensitivity and virulence traits. Here, we investigated the effect of switching on alterations at the cellular structure level of C. tropicalis morphotypes and whether exposure to fluconazole (FLC) in vitro could be associated with these alterations in a morphotype-dependent manner. Candida tropicalis morphotypes included clinical isolate (Parental) and two switch strains (Crepe variant and revertant of Crepe-RC). The minimum inhibitory concentration (MIC50) of fluconazole was determined according to EUCAST. Cell wall porosity, quantification of cell wall components, cell size/complexity, and expression of ERG11 and CDR1 genes in morphotypes pre- and post-exposure to fluconazole were determined. Crepe and RC showed an eightfold higher MIC50 (1 µg/ml) than the Parental (0.125 µg/ml). Exposure to FLC resulted in twofold higher MIC50 for Parental and RC. The Crepe variant exhibited a fourfold higher expression of ERG11, and the RC showed 10-fold higher expression of CDR1 than the clinical isolate. Switch strains showed reduced cell wall porosity compared to Parental, and exposure to FLC resulted in a significant reduction in the porosity of Parental and RC cells. Furthermore, phenotypic switching affected cell wall β-1,3-glucan and chitin contents in a morphotype-dependent manner. Our findings indicate that switching affects cellular structure in C. tropicalis and the occurrence of differential alterations between the clinical isolate and its switched states in response to fluconazole exposure.

Keywords: CDR1; ERG11; cell wall; fluconazole; phenotypic switching.