Enhancement of the antifungal activity of some antimycotics by farnesol and reduction of Candida albicans pathogenicity in a quail model experiment

Nadezhda Sachivkina; Alexander Senyagin; Irina Podoprigora; Elena Vasilieva; Olga Kuznetsova; Arfenia Karamyan; Alfia Ibragimova; Natalia Zhabo; Maria Molchanova

doi:10.14202/vetworld.2022.848-854

Enhancement of the antifungal activity of some antimycotics by farnesol and reduction of Candida albicans pathogenicity in a quail model experiment

Vet World. 2022 Apr;15(4):848-854. doi: 10.14202/vetworld.2022.848-854. Epub 2022 Apr 8.

Authors

Nadezhda Sachivkina¹, Alexander Senyagin¹, Irina Podoprigora¹, Elena Vasilieva¹, Olga Kuznetsova², Arfenia Karamyan³, Alfia Ibragimova^{4

5}, Natalia Zhabo⁵, Maria Molchanova⁵

Affiliations

¹ Department of Microbiology and Virology, Institute of Medicine, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia.
² Department of Biochemistry, Institute of Medicine, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia.
³ Department of Veterinary Medicine, Agrarian Technological Institute, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia.
⁴ Department of General Pharmaceutical and Biomedical Technologies, Institute of Medicine, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia.
⁵ Department of Foreign Languages, Institute of Medicine, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia.

Abstract

Background and aim: Clinical strains of microorganisms, including pathogenic yeast-like fungi (YLF), are resistant to currently used antifungal agents. Thus, it is relevant to study the combinations of existing antimicrobial drugs and a medicinal extract of plant origin (farnesol). In previous studies, farnesol showed a relatively strong anti-biofilm effect against Candida albicans. This study aimed to determine how much the resistance profile of non-biofilm microorganisms can change.

Materials and methods: Six clinical isolates of C. albicans and one reference strain were used to study the interaction of farnesol with the most used antimycotics. To determine the sensitivity of YLF to antimycotic drugs, such as nystatin (50 μg), amphotericin B (10 μg), ketoconazole (10 μg), clotrimazole (10 μg), voriconazole (10 μg), fluconazole (25 μg), miconazole (10 μg), and intraconazole (10 μg), the classic disk diffusion method was used. In the second stage, one of the six strains was used to simulate candidiasis of the gastrointestinal tract in an in vivo quail model. As an unusual experimental design, this study investigated the effects of pretreated C. albicans in quails, not the in vivo pathogenicity of C. albicans, after treatment with farnesol.

Results: The resistance profiles of Candida strains did not improve with farnesol in all strains. All concentrations of farnesol (100, 50, and 25 μM) demonstrated a fungistatic effect (i.e., an increase in drug sensitivity) in 23 of 56 (7×8) cases (41%). The remaining 54% demonstrated no changes in the resistance to antifungal drugs or deterioration of the indicators in rare cases (5%). At 100 μM farnesol, sensitivity improved in 33 of 56 cases (59%). Candidiasis or the severity of clinical disease of the quail digestive tract developed to a lesser extent if fungi were treated with farnesol.

Conclusion: Farnesol does not always show a positive result on single cells without biofilm in the laboratory. However, in a biofilm or an in vivo model with biofilms, farnesol can be considered a new antimycotic drug or an additive to existing antimycotics.

Keywords: Candida albicans; amphotericin B; antimycotics; clotrimazole; farnesol; fluconazole; intraconazole; ketoconazole; miconazole; nystatin; quail model; quorum sensing; voriconazole.