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The Absence of PDR16 Gene Restricts the Overexpression of CaSNQ2 Gene in the Presence of Fluconazole in Candida albicans

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Abstract

In yeast, the PDR16 gene encodes one of the PITP proteins involved in lipid metabolism and is regarded as a factor involved in clinical azole resistance of fungal pathogens. In this study, we prepared Candida albicans CaPDR16/pdr16Δ and Capdr16Δ/Δ heterozygous and homozygous mutant strains and assessed their responses to different stresses. The CaPDR16 deletion strains exhibited increased susceptibility to antifungal azoles and acetic acid. The addition of Tween80 restored the growth of Capdr16 mutants in the presence of azoles. However, the PDR16 gene deletion has not remarkable influence on sterol profile or membrane properties (membrane potential, anisotropy) of Capdr16Δ and Capdr16Δ/Δ mutant cells. Changes in halotolerance of C. albicans pdr16 deletion mutants were not observed. Fluconazole treatment leads to increased expression of ERG genes both in the wild-type and Capdr16Δ and Capdr16Δ/Δ mutant cells, and the amount of ergosterol and its precursors remain comparable in all three strains tested. Fluconazole treatment induced the expression of ATP-binding cassette transporter gene CaSNQ2 and MFS transporter gene CaTPO3 in the wild-type strain but not in the Capdr16Δ and Capdr16Δ/Δ mutants. The expression of CaSNQ2 gene markedly increased also in cells treated with hydrogen peroxide irrespective of the presence of CaPdr16p. CaPDR16 gene thus belongs to genes whose presence is required for full induction of CaSNQ2 and CaTPO3 genes in the presence of fluconazole in C. albicans.

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Acknowledgements

We gratefully acknowledge financial support from the Slovak Grant Agency of Science (Grant Nos. VEGA 2/0111/15 and VEGA 1/0697/18).

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  1. Eduard Goffa

    Present address: Department of Genetics, Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy Sciences, Dúbravská cesta 9, 84505, Bratislava, Slovak Republic

Authors and Affiliations

  1. Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 842 15, Bratislava 4, Slovak Republic

    Alexandra Bencova, Eduard Goffa, Nora Toth Hervay & Yvetta Gbelska

  2. Faculty of Mathematics, Physics and Informatics, Comenius University in Bratislava, Mlynská dolina F1, 842 48, Bratislava, Slovak Republic

    Marcela Morvova

  3. Institute of Animal Biochemistry and Genetics CBS SAS, Dúbravská cesta 9, 840 05, Bratislava, Slovak Republic

    Martin Valachovic & Peter Griač

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11046_2020_459_MOESM1_ESM.tif

Suppl. Fig. 1. Growth of wild-type and isogenic Capdr16Δ deletion mutant strains in the presence of alkali metal cations. Tenfold serial dilutions of overnight cultures were prepared and 5 µl aliquots spotted onto YPD plates and incubated at 28 °C for 2 days. (TIF 4389 kb)

Suppl. 1 Table Oligonucleotides used in this study (DOCX 14 kb)

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Bencova, A., Goffa, E., Morvova, M. et al. The Absence of PDR16 Gene Restricts the Overexpression of CaSNQ2 Gene in the Presence of Fluconazole in Candida albicans. Mycopathologia 185, 455–465 (2020). https://doi.org/10.1007/s11046-020-00459-4

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