# Untargeted Metabolomic Analysis of Cell-Free Supernatants (CFSs) from Different Clinical Isolates of Saccharomyces cerevisiae and Their Effects on Candida albicans Virulence

## TL;DR

This study explores how cell-free supernatants from different yeast strains can reduce the harmful effects of a fungal pathogen.

## Contribution

The study identifies specific metabolites in cell-free supernatants that may reduce Candida albicans virulence.

## Key findings

- Cell-free supernatants from S. cerevisiae isolates reduced Candida albicans adhesion and biofilm formation.
- Metabolomic analysis revealed overexpression of N-acetyl-DL-tryptophan and related compounds in fecal isolates.
- Supernatants from fecal isolates contained unique molecules like inosine and specific dipeptides.

## Abstract

Saccharomyces cerevisiae probiotic properties are effective for the treatment of infections by the opportunistic pathogen Candida albicans. Here, we assessed the anti-Candida effect of cell-free supernatants (CFSs) from three different fecal isolates and one ATCC strain of S. cerevisiae. We evaluated C. albicans growth inhibition through CFUs, and the impairment of virulence factors (adhesion, biofilm formation, and metabolic activity) by crystal violet and XTT assays. An untargeted metabolomic analysis of the CFSs was also performed. The CFSs moderately reduced C. albicans growth, but they could impair C. albicans virulence by reducing its capacity to adhere and to form a biofilm, and by decreasing the metabolic activity of biofilm-embedded fungal cells. The untargeted metabolomic analysis indicated an overexpression of N-acetyl-DL-tryptophan and other molecules derived from its metabolism (kynurenic acid and indole-3-acrylic acid), the dipeptides glycyl-L-leucine, prolyl-leucine, and γ-L-glutamyl-L-leucine, and the unconventional nucleotide inosine in the CFSs from fecal isolates, as compared to the reference strain. Further studies are warranted to better characterize the metabolome of these CFSs. Should the effects described here also be confirmed in vivo, the possible future employment of S. cerevisiae CFSs as a postbiotic aid to the current antifungal therapy may be considered.