Virulence Factors and in-Host Selection on Phenotypes in Infectious Probiotic Yeast Isolates (Saccharomyces 'boulardii').

Alexandra Imre,Dániel Nemes,Károly Kovács,Walter P Pfliegler,Attila Gácser,Zoltán Farkas,Ilona Dóczi,László Majoros,Kitti Pázmándi,Ágnes Jakab,István Pócsi,Ildikó Bácskay,Renátó Kovács,Hanna Viktória Rácz,Tünde Fekete

doi:10.3390/jof7090746

Abstract

Saccharomyces yeast probiotics (S. ‘boulardii’) have long been applied in the treatment of several gastrointestinal conditions. Despite their widespread use, they are rare opportunistic pathogens responsible for a high proportion of Saccharomyces mycosis cases. The potential virulence attributes of S. ‘boulardii’ as well as its interactions with the human immune system have been studied, however, no information is available on how these yeasts may change due to in-host evolution. To fill this gap, we compared the general phenotypic characteristics, cell morphology, virulence factors, epithelial and immunological interactions, and pathogenicity of four probiotic product samples, two mycosis, and eight non-mycosis samples of S. ‘boulardii’. We assessed the characteristics related to major steps of yeast infections. Mycosis and non-mycosis isolates both displayed novel characters when compared to the product isolates, but in the case of most virulence factors and in pathogenicity, differences were negligible or, surprisingly, the yeasts from products showed elevated levels. No isolates inflicted considerable damage to the epithelial model or bore the hallmarks of immune evasion. Our results show that strains in probiotic products possess characteristics that enable them to act as pathogens upon permissive conditions, and their entry into the bloodstream is not due to active mechanisms but depends on the host. Survival in the host is dependent on yeast phenotypic characteristics which may change in many ways once they start evolving in the host. These facts call attention to the shortcomings of virulence phenotyping in yeast research, and the need for a more thorough assessment of probiotic use.

Highlights

Throughout history, Saccharomyces cerevisiae has been an indispensable fungus in agriculture and the food industry [1,2]
Based on the origin and the pathogenic potential of the isolates we grouped the isolates into three groups: commercial (PY0001, PY0002, PY0003, PY0004), mycosis causing (DE6507, DE35762), and non-mycosis clinical isolates (DE27020, DE3912, DE42533, DE42807, DE45866, 465/2018, 551/2018, 2251/2018)
The isolates tested in our study showed negligible pathogenic interactions with the epithelium overall (Figure 3)

Summary

Introduction

Throughout history, Saccharomyces cerevisiae has been an indispensable fungus in agriculture and the food industry [1,2]. ‘boulardii’ is applied commonly as a probiotic both for human use and even for livestock [3,4,5,6,7] It is by far the leading probiotic yeast in the world [8] and its probiotic properties have been demonstrated in more than 80 randomized clinical trials for the strain S. ‘boulardii’ have found that isolates from different sources show little variation and most of them have a diploid euploid genome [11,12] This widely used and thoroughly researched probiotic yeast is an opportunistic pathogen. We demonstrated that probiotic-derived clinical yeasts are common among S. cerevisiae isolates collected from a single Hungarian hospital over the course of three years (seven isolates, including two fungemia cases, were probiotic-derived out of 15 S. cerevisiae infections [16])

Methods

Results

Discussion

Conclusion