Capric acid secreted by Saccharomyces boulardii influences the susceptibility of Candida albicans to fluconazole and amphotericin B

Jakub Suchodolski,Daria Derkacz,Przemysław Bernat,Anna Krasowska

doi:10.1038/s41598-021-86012-9

Jakub Suchodolski, Daria Derkacz + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-86012-9

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Journal: Scientific Reports	Publication Date: Mar 22, 2021
Citations: 12	License type: open-access

Affiliation: University of Wrocław, University of Łódź

Abstract

The effect of capric acid, secreted by the probiotic yeasts Saccharomyces boulardii, was evaluated on the activities of fluconazole (FLC) and amphotericin B (AMB) against pathogenic Candida albicans fungus. The findings indicated that capric acid may be a promising additive for use in combination with FLC. A FLC-capric acid combination led to reduced efflux activity of multidrug resistance (MDR) transporter Cdr1p by causing it to relocalize from the plasma membrane (PM) to the interior of the cell. The above effect occurred due to inhibitory effect of FLC-capric acid combination of ergosterol biosynthesis. However, capric acid alone stimulated ergosterol production in C. albicans, which in turn generated cross resistance towards AMB and inhibited its action (PM permeabilization and cytoplasm leakage) against C. albicans cells. This concluded that AMB should not be administered among dietary supplements containing capric acid or S. boulardii cells.

Highlights

The effect of capric acid, secreted by the probiotic yeasts Saccharomyces boulardii, was evaluated on the activities of fluconazole (FLC) and amphotericin B (AMB) against pathogenic Candida albicans fungus
In this study we aimed to investigate the effect of capric acid on the antifungal properties of FLC and AMB against C. albicans
The effect of capric acid treatment was evaluated against the inhouse generated C. albicans KS028 strain, which features an ERG11 gene deletion, depriving the cells of ergosterol (Fig. 1A)

Summary

Introduction

The effect of capric acid, secreted by the probiotic yeasts Saccharomyces boulardii, was evaluated on the activities of fluconazole (FLC) and amphotericin B (AMB) against pathogenic Candida albicans fungus. A FLC-capric acid combination led to reduced efflux activity of multidrug resistance (MDR) transporter Cdr1p by causing it to relocalize from the plasma membrane (PM) to the interior of the cell. Capric acid alone stimulated ergosterol production in C. albicans, which in turn generated cross resistance towards AMB and inhibited its action (PM permeabilization and cytoplasm leakage) against C. albicans cells. There is limited range of antifungal drug classes available to combat candidiasis One such drug class includes azoles, which inhibit ergosterol biosynthesis by targeting cytochrome P-450 lanosterol 14α-demethylase (CYP51A1, Erg11p) encoded by the ERG11 gene[4]. Probiotic yeast Saccharomyces boulardii, is known to produce caproic (C6:0), caprylic (C8:0) and capric (C10:0)

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