Effects of fluconazole on Candida glabrata biofilms and its relationship with ABC transporter gene expression

Abstract

Candida glabrata has emerged as the second most prevalent fungal pathogen and its ability to form biofilms has been considered one of the most important virulence factors, since biofilms present a high tolerance to antifungal agents used in fungal infection treatment. The mechanisms of biofilm tolerance to antifungal agents remain poorly understood. Thus, the aim of this study was to evaluate the effects of fluconazole (FLU) in the formation and control of C. glabrata biofilms and its relation with the expression of genes encoding for ABC transporters, CDR1, SNQ2, and PDR1. For that, MICs values for seven C. glabrata strains were determined and the FLU effect against C. glabrata biofilms evaluated by total biomass quantification and CFUs enumeration. Matrices from biofilms were analyzed in terms of proteins, carbohydrates and DNA content. ABC transporters genes expression was analyzed for quantitative real-time PCR. Additionally to the high amounts of proteins and carbohydrates detected in the extracellular matrices in the presence of FLU, this work showed that the overexpression of efflux pumps is a possible mechanism of biofilm tolerance to FLU and this phenomenon alters the structure of C. glabrata biofilms by creating cell clusters.