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

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SHORT COMMUNICATION

Modulation of ERG Genes Expression in Clinical Isolates of Candida tropicalis Susceptible and Resistant to Fluconazole and Itraconazole Maria Cla´udia Silva . De´bora Cardozo Bonfim Carbone . Pedro Fernando Diniz . Fabrı´cio Freitas Fernandes . Carlos Alessandro Fuzo . Carolina Santos Pereira Cardoso Trindade . Marilene Rodrigues Chang . Joa˜o Santana Silva

Received: 17 February 2020 / Accepted: 27 May 2020 / Published online: 4 June 2020 Ó Springer Nature B.V. 2020

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

Maria Cla´udia Silva, De´bora Cardozo Bonfim Carbone contributed equally to this study Handling Editor: Weida Liu.

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 upregulation 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. Keywords Candida tropicalis  ERG genes  Efflux pump genes  Azole drugs

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11046-020-00465-6) contains supplementary material, which is available to authorized users. M. C. Silva  J. S. Silva Department of Biochemistry and Immunology, Ribeira˜o Preto Medical School, University of Sa˜o Paulo, Ribeira˜o Preto, SP, Brazil

F. Freitas Fernandes Department of Cellular and Molecular Biology, Preto Medicine School, University of Sa˜o Paulo, Ribeira˜o Preto, SP, Brazil

D. Cardozo Bonfim Carbone  C. Santos Pereira Cardoso Trindade  J. S. Silva Post-Graduation Program in Biotechnology, Universidade Cato´lica Dom Bosco, Campo Grande, MS, Brazil

C. A. Fuzo  J. S. Silva (&) Fiocruz-Bi-Institutional Translational Medicine Plataform, Ribeira˜o Preto Medical School, University of Sa˜o Paulo, Avenida Bandeirantes, 3900, CEP 14049-900 Ribeira˜o Preto, SP, Brazil e-mail: [email protected]

P. F. Diniz  M. Rodrigues Chang Post-Graduation Program in Infectious and Parasitic Diseases, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil

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Introduction As a result of the increasing number of available immunosuppressive therapies, as well as antibioticsinduced reduction of the microbiota, damage in gastrointestinal mucosa and invasive surgical procedures, the occurrence of opportunistic fungal infections among human patients has significantly increased in t