Antifungal Agent 4-AN Changes the Genome-Wide Expression Profile, Downregulates Virulence-Associated Genes and Induces Necrosis in <i>Candida albicans</i> Cells
Aleksandra Martyna,
Maciej Masłyk,
Monika Janeczko,
Elżbieta Kochanowicz,
Bartłomiej Gielniewski,
Aleksandra Świercz,
Oleg M. Demchuk,
Konrad Kubiński
Affiliations
Aleksandra Martyna
Department of Molecular Biology, Institute of Biological Sciences, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
Maciej Masłyk
Department of Molecular Biology, Institute of Biological Sciences, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
Monika Janeczko
Department of Molecular Biology, Institute of Biological Sciences, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
Elżbieta Kochanowicz
Department of Molecular Biology, Institute of Biological Sciences, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
Bartłomiej Gielniewski
Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland
Aleksandra Świercz
Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznań, Poland
Oleg M. Demchuk
Pharmaceutical Research Institute, Rydygiera Street 8, 01-793 Warsaw, Poland
Konrad Kubiński
Department of Molecular Biology, Institute of Biological Sciences, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland
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 upregulation was observed in the case of genes involved in cell stress, while the highest downregulation 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 C. albicans cells.
