Global analysis of Saccharomyces cerevisiae growth in mucin

Abstract

Metagenomic profiling of the human gut microbiome has discovered DNA from dietary yeasts like Saccharomyces cerevisiae. However, it is unknown if the S. cerevisiae detected by common metagenomic methods are from dead dietary sources, or from live S. cerevisiae colonizing the gut similar to their close relative Candida albicans. While S. cerevisiae can adapt to minimal oxygen and acidic environments, it has not been explored whether this yeast can metabolize mucin, the large, gel-forming, highly glycosylated proteins representing a major source of carbon in the gut mucosa. We reveal that S. cerevisiae can utilize mucin as their main carbon source, as well as perform both a transcriptome analysis and a chemogenomic screen to identify biological pathways required for this yeast to grow optimally in mucin. In total, 739 genes demonstrate significant differential expression in mucin culture, and deletion of 21 genes impact growth in mucin. Both screens suggest that mitochondrial function is required for proper growth in mucin, and through secondary assays we determine that mucin exposure induces mitogenesis and cellular respiration. We further show that deletion of an uncharacterized ORF, YCR095W-A, led to dysfunction in mitochondrial morphology and oxygen consumption in mucin. Lastly, we demonstrate that Yps7, an aspartyl protease and homologue to mucin-degrading proteins in C. albicans, is important for growth on mucin. Collectively, our work serves as the initial step towards establishing how this common dietary fungus can survive in the mucus environment of the human gut.

Yeast adapts to diverse ecological niches driven by genomics and metabolic reprogramming

“…For example, inositol phosphate metabolism, which plays an important role in membrane synthesis 42 and stress responses 46 , experienced significant reaction loss in domesticated clades such as French dairy and Wine/European (subclade 1), which may be related to the adaptation to high osmotic stress conditions during domestication. As another example, the steroid biosynthesis, oxygen-dependent in S. cerevisiae 47 , is consistently inactive in strains from French Guiana human clade 48 , which mainly grow under low-oxygen conditions.…”

“…4b). Furthermore, strains from these three clades typically encounter oxygen limitation in their biological habitats 48 .…”

“…Interestingly, the human clade also exhibits a higher ethanol secretion compared to the wild strains, potentially due to its adaptive evolution in an oxygen-limited human gut environment (Supplementary Fig. 7b) 48 . Overall, the reliability of our pipeline in condition-specific flux simulation is demonstrated by the precise predictions for growth and ethanol secretion of S. cerevisiae strains from different clades.…”

The NIH Comparative Genomics Resource: addressing the promises and challenges of comparative genomics on human health

“…Despite the well-characterized S. cerevisiae genome, it was historically difficult to determine if its detection in fecal samples was due to live colonization within microbiome or merely dead cells from dietary consumption. Comparative genomics was used to identify a homolog between S. cerevisiae to C. albicans (Yps7, an aspartyl protease) that is important for fungal growth on mucin of the human intestinal track, thus suggesting the viability of S. cerevisiae colonization in the human microbiome [ 42 ].…”