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Antifungal activity of β-lapachone against a fluconazole-resistant Candida auris strain

  • Medicine and Public Health - Research Paper
  • Published:
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Abstract

Candida spp. can be found in the human microbiome. However, immunocompromised patients are likely to develop invasive Candida infections, with mortality rates higher than 50%. The discovery of C. auris, a species that rapidly acquire antifungal resistance, increased the concern about Candida infections. The limited number of antifungal agents and the high incidence of resistance to them make imperative the development of new antifungal drugs. β-lapachone is a biological active naphthoquinone that displays antifungal activity against C. albicans and C. glabrata. The aim of this study was to evaluate if this substance affects C. auris growth and elucidate its mechanism of action. A fluconazole-resistant C. auris isolate was used in this study. The antifungal activity of β-lapachone was determined through microbroth dilution assays, and its mechanism of action was evaluated using fluorescent probes. Interaction with fluconazole and amphotericin B was assessed by disk diffusion assay and checkerboard. β-lapachone inhibited planktonic C. auris cell growth by 92.7%, biofilm formation by 84.9%, and decrease the metabolism of preformed biofilms by 87.1% at 100 µg/ml. At 100 µg/ml, reductions of 30% and 59% of Calcofluor White and Nile red fluorescences were observed, indicating that β-lapachone affects cell wall chitin and neutral lipids content, respectively. Also, the ratio 590 nm/529 nm of JC-1 decreased 52%, showing that the compound affects mitochondria. No synergism was observed between β-lapachone and fluconazole or amphotericin B. Data show that β-lapachone may be a promising candidate to be used as monotherapy to treat C. auris resistant infections.

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Funding

This study was supported by Universidade Estácio de Sá (UNESA) − Bolsa de Pesquisa Produtividade. This study was also financed by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior– Brazil (CAPES)– Finance Code 001.

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Authors and Affiliations

  1. Universidade Estácio de Sá, 24020-340, Centro, Niterói, RJ, Brazil

    Daniel Clemente de Moraes

  2. Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro-RJ, Brazil

    Daniel Clemente de Moraes, Rodrigo Rollin-Pinheiro, Levy Tenório Sousa Domingos, Eliana Barreto-Bergter & Antonio Ferreira-Pereira

  3. Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro-RJ, Brazil

    Maria do Carmo Freire Ribeiro Pinto

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  1. Daniel Clemente de Moraes
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Contributions

DCDM: Conception and design of the study; acquisition, analysis and interpretation of data; drafting the article. RR-P: acquisition of data, critical revision of the article. MDCFRP: acquisition of data. LTSD: acquisition of data. EB-B: final approval of the version to be submitted. AF-P: conception and design of the study; critical revision of the article and final approval of the version to be submitted.

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Correspondence to Antonio Ferreira-Pereira.

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de Moraes, D.C., Rollin-Pinheiro, R., Pinto, M.d.C.F.R. et al. Antifungal activity of β-lapachone against a fluconazole-resistant Candida auris strain. Braz J Microbiol (2024). https://doi.org/10.1007/s42770-024-01375-1

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