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.
Highlights
Candida auris is an emerging fungal pathogen causing outbreaks in healthcare settings with unacceptably high mortality rates ranging from 28 to 78% depending on the country (JefferySmith et al, 2017; Eyre et al, 2018)
This study examines the effect of farnesol exposure on growth, biofilm production, oxidative stress-related enzyme production, triazole susceptibility and virulence of C. auris, in order to explore the background of the previously observed antifungal effect
Farnesol exposure resulted in significantly higher phospholipase activity for C. albicans (Pz values were 0.48 ± 0.04 and 0.42 ± 0.02 for untreated control and farnesol-exposed cells, respectively (p < 0.01); the precipitation zones (Pz) values were statistically comparable in case of C. auris (Pz values were 0.9 ± 0.04 and 0.89 ± 0.05 for untreated control and farnesol-exposed cells, respectively (p > 0.05)
Summary
Candida auris is an emerging fungal pathogen causing outbreaks in healthcare settings with unacceptably high mortality rates ranging from 28 to 78% depending on the country (JefferySmith et al, 2017; Eyre et al, 2018). 39 countries have reported C. auris associated infections (Jeffery-Smith et al, 2017; Eyre et al, 2018; Kean et al, 2020). Nosocomial C. auris outbreaks were reported from several countries including India, South Africa, Venezuela, Pakistan, and the United States (Lockhart et al, 2017; Vallabhaneni et al, 2017; Belkin et al, 2018). Genetic analyses revealed more genetically unrelated clonal populations across three different continents. These clades are commonly classified as South African, South Asian, East Asian, and South American clades (Lockhart et al, 2017). A recent study described a fifth C. auris clade in Iran from patient who never traveled outside that country (Abastabar et al, 2019; Chow et al, 2019)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
