Heme Oxygenase-1 (<i>HMX1</i>) Loss of Function Increases the In-Host Fitness of the <i>Saccharomyces ‘boulardii’</i> Probiotic Yeast in a Mouse Fungemia Model

Abstract

The use of yeast-containing probiotics is on the rise; however, these products occasionally cause fungal infections and possibly even fungemia among susceptible probiotic-treated patients. The incidence of such cases is probably underestimated, which is why it is important to delve deeper into the pathomechanism and the adaptive features of S. ‘boulardii’. Here in this study, the potential role of the gene heme oxygenase-1 (HMX1) in probiotic yeast bloodstream-derived infections was studied by generating marker-free HMX1 deletion mutants with CRISPR/Cas9 technology from both commercial and clinical S. ‘boulardii’ isolates. The six commercial and clinical yeasts used here represented closely related but different genetic backgrounds as revealed by comparative genomic analysis. We compared the wild-type isolates against deletion mutants for their tolerance of iron starvation, hemolytic activity, as well as kidney burden in immunosuppressed BALB/c mice after lateral tail vein injection. Our results reveal that the lack of HMX1 in S. ‘boulardii’ significantly (p S. ‘boulardii’ strains should not only take strain-to-strain variation into account, but also avoid extrapolating in vitro results to in vivo virulence factor determination.

Keywords

• fungaemia
• heme oxygenase
• hemolysis
• iron starvation
• genomics
• probiotic yeast