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Mechanism of Action and Synergistic Effect of Eugenia Uniflora Extract in Candida Spp

Abstract

The limited arsenal of antifungal drugs have prompted the search for novel molecules with biological activity. This study aimed to characterize the antifungal mechanism of action of Eugenia uniflora extract and its synergistic activity with commercially available antifungal drugs on the following Candida species: C. albicans, C. tropicalis, C. glabrata, C. parapsilosis and C. dubliniensis. In silico analysis was performed to predict antifungal activity of the major compounds present in the extract. Minimal inhibitory concentrations (MICs) were determined in the presence of exogenous ergosterol and sorbitol. Yeast cells were grown in the presence of stressors. The loss of membrane integrity was assessed using propidium iodide staining (fluorescence emission). Synergism between the extract and antifungal compounds (in addition to time kill-curves) was determined. Molecular docking revealed possible interactions between myricitrin and acid gallic and enzymes involved in ergosterol and cell wall biosynthesis. Candida cells grown in the presence of the extract with addition of exogenous ergosterol and sorbitol showed 2 to 8-fold increased MICs. Strains treated with the extract revealed greater loss of membrane integrity when compared to their Fluconazole counterparts, but this effect was less pronounced than the membrane damage caused by Amphotericin B. The extract also made the strains more susceptible to Congo red and Calcofluor white. A synergistic action of the extract with Fluconazole and Micafungin was observed. The E. uniflora extract may be a viable option for the treatment of Candida infections.

References
1.
Sun F, Li M, Gu L, Wang M, Yang M . Recent progress on anti-Candida natural products. Chin J Nat Med. 2021; 19(8):561-579. DOI: 10.1016/S1875-5364(21)60057-2. View

2.
Newman D, Cragg G . Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J Nat Prod. 2020; 83(3):770-803. DOI: 10.1021/acs.jnatprod.9b01285. View

3.
Gil-Bona A, Marcela Parra-Giraldo C, Hernaez M, Reales-Calderon J, Solis N, Filler S . Candida albicans cell shaving uncovers new proteins involved in cell wall integrity, yeast to hypha transition, stress response and host-pathogen interaction. J Proteomics. 2015; 127(Pt B):340-351. PMC: 4721921. DOI: 10.1016/j.jprot.2015.06.006. View

4.
Schwartz S, Kontoyiannis D, Harrison T, Ruhnke M . Advances in the diagnosis and treatment of fungal infections of the CNS. Lancet Neurol. 2018; 17(4):362-372. DOI: 10.1016/S1474-4422(18)30030-9. View

5.
Cavalheiro M, Teixeira M . Biofilms: Threats, Challenges, and Promising Strategies. Front Med (Lausanne). 2018; 5:28. PMC: 5816785. DOI: 10.3389/fmed.2018.00028. View