Portrait of Matrix Gene Expression in Candida glabrata Biofilms with Stress Induced by Different Drugs

Abstract

(1) Background: Candida glabrata is one of the most significant Candida species associated with severe cases of candidiasis. Biofilm formation is an important feature, closely associated with antifungal resistance, involving alterations of gene expression or mutations, which can result in the failure of antifungal treatments. Hence, the main goal of this work was to evaluate the role of a set of genes, associated with matrix production, in the resistance of C. glabrata biofilms to antifungal drugs. (2) Methods: the determination of the expression of BGL2, XOG1, FKS1, FKS2, GAS2, KNH1, UGP1, and MNN2 genes in 48-h biofilm's cells of three C. glabrata strains was performed through quantitative real-time PCR (RT-qPCR), after contact with Fluconazole (Flu), Amphotericin B (AmB), Caspofungin (Csf), or Micafungin (Mcf). (3) Results: Mcf induced a general overexpression of the selected genes. It was verified that the genes related to the production of β-1,3-glucans (BGL2, XOG1, GAS2) had the highest expressions. (4) Conclusion: though β-1,6-glucans and mannans are an essential part of the cell and biofilm matrix, C. glabrata biofilm cells seem to contribute more to the replacement of β-1,3-glucans. Thus, these biopolymers seem to have a greater impact on the biofilm matrix composition and, consequently, a role in the biofilm resistance to antifungal drugs.

Keywords: Candida; Candida glabrata; biofilms; drug resistance; gene expression; matrix.

Figure 1

Real-time PCR expression profiling of BGL2, XOG1, GAS2, FKS1, FKS2, KNH1, UGP1, and MNN2 genes in biofilm cells of Candida glabrata ATCC2001 (reference strain, in bold) (a), C. glabrata 562123 (b), and C. glabrata 534784 (c) in the presence of antifungal drugs. The heatmap was generated by a log transformation of the RT-qPCR data and the fold-change (FC) expression determined through 2^−ΔC_T. The numerical scale on the right represents the FC. (Control: non-treated cells).