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.
Highlights
Fungal infections continue to increase worldwide, among immunosuppressed patients, individuals under prolonged hospitalization, catheterization, or continued antimicrobial treatments [1,2,3]
Candidaemia related to C. glabrata has been increasing in the last years in parallel with its high drug resistance, to the azole antifungal class [1,20,66]
In order to stress C. glabrata biofilm cells, four antifungals were applied in pre-formed biofilms, and an evaluation of biofilms’ matrix gene expression was performed and compared with the expression of a housekeeping gene
Summary
Fungal infections continue to increase worldwide, among immunosuppressed patients, individuals under prolonged hospitalization, catheterization, or continued antimicrobial treatments [1,2,3]. Though C. glabrata does not have the capacity to form hyphae and pseudohyphae or to secret proteases, this species has other virulence factors, such as the ability to secrete phospholipases, lipases, and haemolysins and, importantly, the capacity to form biofilms [6,7,8]. These factors highly contribute to a high aggressiveness, resulting in a low therapeutic response and severe cases of recurrent candidiasis [8,9]. C. glabrata has shown to form a compact biofilm structure in different multilayers [6,7], with proteins, carbohydrates, and ergosterol into their matrices [6,7,13]
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