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Modulation of ERG Genes Expression in Clinical Isolates of Candida tropicalis Susceptible and Resistant to Fluconazole and Itraconazole

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Abstract

Candida tropicalis is a non-albicans Candida specie that causes candidosis in several countries, including Brazil. However, little is known about the mechanisms of drug resistance in C. tropicalis infections. In this study, we used clinical isolates of C. tropicalis susceptible as well as resistant to either Fluconazole or Itraconazole to assess the relationship between drug resistance and the expression of ERG and efflux pump genes. Our results showed that the main mechanism of resistance against both Fluconazole and Itraconazole in this specie is through the up-regulation of ERG rather than that of the efflux pump genes. We demonstrated that, although pre-treatment with azole drugs increases the expression of both ERG6 and ERG11 genes, the resistant or susceptible dose-dependent (SDD) samples are able to maintain high expression levels of these genes for longer periods of time than the susceptible samples.

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Acknowledgements

This research received funding from FAPESP under grant agreement number 2013/08216-2 (Center for Research in Inflammatory Disease—CRID), from National Council for Scientific and Technological Development (CNPq) under Grant Number 308490/2014-5 and also from Coordination for the Improvement of Higher Education Personnel (CAPES) under finance code 001.

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Author notes

  1. Maria Cláudia Silva, Débora Cardozo Bonfim Carbone contributed equally to this study

Authors and Affiliations

  1. Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil

    Maria Cláudia Silva & João Santana Silva

  2. Post-Graduation Program in Biotechnology, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil

    Débora Cardozo Bonfim Carbone, Carolina Santos Pereira Cardoso Trindade & João Santana Silva

  3. Post-Graduation Program in Infectious and Parasitic Diseases, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil

    Pedro Fernando Diniz & Marilene Rodrigues Chang

  4. Department of Cellular and Molecular Biology, Preto Medicine School, University of São Paulo, Ribeirão Preto, SP, Brazil

    Fabrício Freitas Fernandes

  5. Fiocruz-Bi-Institutional Translational Medicine Plataform, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, CEP 14049-900, Ribeirão Preto, SP, Brazil

    Carlos Alessandro Fuzo & João Santana Silva

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  1. Maria Cláudia Silva
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Contributions

MCS, FFF and JSS conceived and designed the experiments. MCS, DCBC, PFD, FFF, CSPCT, CAF and MRC performed the experiments. MCS, FFF and JSS analyzed the data. MCS, FFF and JSS drafted the manuscript. MCS, MRC and JSS reviewed and edited the manuscript. All of the authors have read and approved the final manuscript.

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Correspondence to João Santana Silva.

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Silva, M.C., Cardozo Bonfim Carbone, D., Diniz, P.F. et al. Modulation of ERG Genes Expression in Clinical Isolates of Candida tropicalis Susceptible and Resistant to Fluconazole and Itraconazole. Mycopathologia 185, 675–684 (2020). https://doi.org/10.1007/s11046-020-00465-6

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