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Antifungal agent 4-AN changes the genome-wide expression profile, down-regulates virulence-associated genes, and induces necrosis in Candida albicans cells

ABSTRACT: In the light of the increasing occurrence of antifungal resistance, there is an urgent need to search for new therapeutic strategies to overcome this phenomenon. One of the applied approaches is the synthesis of small-molecule compounds showing antifungal properties. Here we present a continuation of the research on the recently discovered anti-Candida albicans agent 4-AN. Using next generation sequencing and transcriptional analysis, we revealed that the treatment of C. albicans with 4-AN can change the expression profile of a large number of genes. The highest up-regulation was observed in the case of genes involved in cell stress, while the highest down-regulation was shown for genes coding sugar transporters. Real-time PCR analysis revealed 4-AN mediated reduction of the relative expression of genes engaged in fungal virulence (ALS1, ALS3, BCR1, CPH1, ECE1, EFG1, HWP1, HYR1, and SAP1). The determination of the fractional inhibitory concentration index (FICI) showed that the combination of 4-AN with Amphotericin B is synergistic. Finally, flow cytometry analysis revealed that the compound induces mainly necrosis in Candida albicans cells.

ORGANISM(S): Candida albicans

PROVIDER: GSE150837 | GEO | 2020/05/20

REPOSITORIES: GEO

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Antifungal agent 4-AN changes the genome-wide expression profile, down-regulates virulence-associated genes, and induces necrosis in Candida albicans cells

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