Probiotic Yeasts Inhibit Virulence of Non -albicans Candida Species

Abstract

Systemic infections of Candida species pose a significant threat to public health. Toxicity associated with current therapies and emergence of resistant strains present major therapeutic challenges. Here, we report exploitation of the probiotic properties of two novel, food-derived yeasts, Saccharomyces cerevisiae (strain KTP) and Issatchenkia occidentalis (strain ApC), as an alternative approach to combat widespread opportunistic fungal infections. Both yeasts inhibit virulence traits such as adhesion, filamentation, and biofilm formation of several non-albicans Candida species, including Candida tropicalis, Candida krusei, Candida glabrata, and Candida parapsilosis as well as the recently identified multidrug-resistant species Candida auris. They inhibit adhesion to abiotic surfaces as well as cultured colon epithelial cells. Furthermore, probiotic treatment blocks the formation of biofilms of individual non-albicans Candida strains as well as mixed-culture biofilms of each non-albicans Candida strain in combination with Candida albicans. The probiotic yeasts attenuated non-albicans Candida infections in a live animal. In vivo studies using Caenorhabditis elegans suggest that exposure to probiotic yeasts protects nematodes from infection with non-albicans Candida strains compared to worms that were not exposed to the probiotic yeasts. Furthermore, application of probiotic yeasts postinfection with non-albicans Candida alleviated pathogenic colonization of the nematode gut. The probiotic properties of these novel yeasts are better than or comparable to those of the commercially available probiotic yeast Saccharomyces boulardii, which was used as a reference strain throughout this study. These results indicate that yeasts derived from food sources could serve as an effective alternative to antifungal therapy against emerging pathogenic Candida species. IMPORTANCE Non-albicans Candida-associated infections have emerged as a major risk factor in the hospitalized and immunecompromised patients. Besides, antifungal-associated complications occur more frequently with these non-albicans Candida species than with C. albicans. Therefore, as an alternative approach to combat these widespread non-albicans Candida-associated infections, here we showed the probiotic effect of two yeasts, Saccharomyces cerevisiae (strain KTP) and Issatchenkia occidentalis (ApC), in preventing adhesion and biofilm formation of five non-albicans Candida strains, Candida tropicalis, Candida krusei, Candida glabrata, Candida parapsilosis, and Candida auris. The result would influence the current trend of the conversion of conventional antimicrobial therapy into beneficial probiotic microbe-associated antimicrobial treatment.

Candida auris: A Decade of Understanding of an Enigmatic Pathogenic Yeast

“…This will enable us to determine whether C. auris synergises or is antagonized by co-colonising microorganisms. This may form a platform for alternative bio-control opportunities as suggested by recent probiotic studies [74].…”

Saccharomyces cerevisiae-Based Probiotics as Novel Antimicrobial Agents to Prevent and Treat Vaginal Infections

“…Due to these characteristics they provide a considerable advantage over bacterial-origin probiotics. Although many yeast species have been shown to possess the characteristics of a probiotic, such as Kluyveromyces lodderae, Kluyveromyces marxianus (Kumura et al, 2004), Kluyveromyces lactis, Yarrowia lipolytica (Li-Shui et al, 2010), and Issatchenkia occidentalis (Kunyeit et al, 2019). Saccharomyces boulardii and Saccharomyces cerevisiae undoubtedly display the most probiotic properties.…”

“…Many studies have, also, highlighted the beneficial effects of several S. cerevisiae strains on entheropatogenic bacteria (Martins et al, 2005;Perez-Sotelo et al, 2005;Martins et al, 2007;Etienne-Mesmin et al, 2011;Tiago et al, 2012;Sivignon et al, 2015;Roussel et al, 2018), on inflammatory bowel diseases (Pineton de Chambrun et al, 2015;Tiago et al, 2015;Spiller et al, 2016;Cayzeele-Decherf et al, 2017b;Gayathri et al, 2020), and on pathogenic fungi (C. albicans and non-albicans Candida species, Aspergillus flavus; Premanathan et al, 2011;Abdel-Kareem et al, 2019;Kunyeit et al, 2019;Roselletti et al, 2019b). The potential mechanisms described include: inhibition of pathogen growth (Etienne-Mesmin et al, 2011;Roussel et al, 2018;Abdel-Kareem et al, 2019;Roselletti et al, 2019b), inhibition of pathogen adherence to epithelial cells (Perez-Sotelo et al, 2005;Tiago et al, 2012;Sivignon et al, 2015;Roussel et al, 2018;Kunyeit et al, 2019), immunomodulatory activity (Martins et al, 2005;Martins et al, 2007;Sivignon et al, 2015;Tiago et al, 2015;Roussel et al, 2018;Roselletti et al, 2019b), inhibition of filamentation and biofilm development (Kunyeit et al, 2019), and reduction of toxin production (Roussel et al, 2018;Abdel-Kareem et al, 2019).…”

Secondary metabolites from food-derived yeasts inhibit virulence ofCandida albicans

“…C. albicans must first adhere to abiotic surfaces then filament to form a three-dimensional biofilm. Beneficial yeast cell number 10 8 / ml was empirically determined as effective against adhesion of C. albicans SC5314 (Kunyeit et al, 2019). To test the effect of the two food derived yeasts Saccharomyces cerevisiae and Issatchenkia occidentalis (Archana and Anu-Appaiah, 2018) on C. albicans virulence we tested adhesion, filamentation and biofilm formation in vitro.…”

“…boulardii and S. cerevisiae have been shown to prevent the colonization and virulence of C. albicans (Pericolini et al, 2017, Murzyn et al, 2010, Jawhara and Poulain, 2007. We and others have previously reported that secreted factors from food-derived beneficial yeasts inhibited virulence traits of many pathogenic fungi (Kunyeit et al, 2019, Banjara et al, 2016. These food-derived yeasts have been considered beneficial in many cultural settings, yet their molecular mechanism of action has not been identified.…”