ReferenceID 5218

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

Front Microbiol

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

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Reference Id
5218
Evidence Id
21808
Core Evidence Id
21808
Source Reference Id
3711
Herb2 Reference Id
HBREF004508
Subject Paper Key
HBIN026385_32508780
Pubmed Id
32508780
Doi
10.3389/fmicb.2020.00957
Paper Title
In vitro and in vivo Effect of Exogenous Farnesol Exposure Against Candida auris
Paper 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 muM 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 muM) was significantly diminished at 24 h depending on farnesol treatment during biofilm formation (p < 0.001-0.05). Moreover, 300 muM 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 muM 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 muM 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.
Journal
Front Microbiol
Publish Year
2020
Experiment Subject
mouse; adhered farnesol pre-exposed cells; farnesol exposed cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Multidrug-resistant Candida Auris; Disseminated Candidiasis
Paper Title Cn
Paper Title En
In vitro and in vivo Effect of Exogenous Farnesol Exposure Against Candida auris
Bilingual Status
semi_complete