In vitro and in vivo Effect of Exogenous Farnesol Exposure Against Candida auris

Fruzsina Nagy, Eszter Vitális, Ágnes Jakab, Andrew M. Borman, Lajos Forgács, Zoltán Tóth, László Majoros, Renátó Kovács*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

The spreading of multidrug-resistant Candida auris is considered as an emerging global health threat. The number of effective therapeutic regimens is strongly limited; therefore, development of novel strategies is needed. Farnesol is a quorum-sensing molecule with a potential antifungal and/or adjuvant effect; it may be a promising candidate in alternative treatment against Candida species including C. auris. To examine the effect of farnesol on C. auris, we performed experiments focusing on growth, biofilm production ability, production of enzymes related to oxidative stress, triazole susceptibility and virulence. Concentrations ranging from 100 to 300 μM farnesol caused a significant growth inhibition against C. auris planktonic cells for 24 h (p < 0.01–0.05). Farnesol treatment showed a concentration dependent inhibition in terms of biofilm forming ability of C. auris; however, it did not inhibit significantly the biofilm development at 24 h. Nevertheless, the metabolic activity of adhered farnesol pre-exposed cells (75 μM) was significantly diminished at 24 h depending on farnesol treatment during biofilm formation (p < 0.001–0.05). Moreover, 300 μM farnesol exerted a marked decrease in metabolic activity against one-day-old biofilms between 2 and 24 h (p < 0.001). Farnesol increased the production of reactive species remarkably, as revealed by 2′,7′-dichlorofluorescein (DCF) assay {3.96 ± 0.89 [nmol DCF (OD640)–1] and 23.54 ± 4.51 [nmol DCF (OD640)–1] for untreated cells and farnesol exposed cells, respectively; p < 0.001}. This was in line with increased superoxide dismutase level {85.69 ± 5.42 [munit (mg protein)–1] and 170.11 ± 17.37 [munit (mg protein)–1] for untreated cells and farnesol exposed cells, respectively; p < 0.001}, but the catalase level remained statistically comparable between treated and untreated cells (p > 0.05). Concerning virulence-related enzymes, exposure to 75 μM farnesol did not influence phospholipase or aspartic proteinase activity (p > 0.05). The interaction between fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole and farnesol showed clear synergism (FICI ranges from 0.038 to 0.375) against one-day-old biofilms. Regarding in vivo experiments, daily 75 μM farnesol treatment decreased the fungal burden in an immunocompromised murine model of disseminated candidiasis, especially in case of inocula pre-exposed to farnesol (p < 0.01). In summary, farnesol shows a promising therapeutic or adjuvant potential in traditional or alternative therapies such as catheter lock therapy.

Original languageEnglish
Article number957
JournalFrontiers in Microbiology
Volume11
DOIs
Publication statusPublished - 20 May 2020

Bibliographical note

Publisher Copyright:
© Copyright © 2020 Nagy, Vitális, Jakab, Borman, Forgács, Tóth, Majoros and Kovács.

Keywords

  • biofilm
  • in vivo
  • oxidative stress
  • quorum-sensing
  • synergy
  • therapy
  • triazoles
  • virulence

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