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The yeast  Saccharomyces boulardii  has been used worldwide as a popular, commercial probiotic, but the basis of its probiotic action remains obscure. It is considered conspecific with budding yeast  Saccharomyces cerevisiae , which is generally used in classical food applications. They have an almost identical genome sequence, making the genetic basis of probiotic potency in  S. boulardii  puzzling. We now show that  S. boulardii  produces at 37°C unusually high levels of acetic acid, which is strongly inhibitory to bacterial growth in agar-well diffusion assays and could be vital for its unique application as a probiotic among yeasts. Using pooled-segregant whole-genome sequence analysis with  S. boulardii  and  S. cerevisiae  parent strains, we succeeded in mapping the underlying QTLs and identified mutant alleles of  SDH1  and  WHI2  as the causative alleles. Both genes contain a SNP unique to  S. boulardii  ( sdh1  F317Y  and  whi2  S287* ) and are fully responsible for its high acetic acid production.  S. boulardii  strains show different levels of acetic acid production, depending on the copy number of the  whi2  S287*  allele. Our results offer the first molecular explanation as to why  S. boulardii  could exert probiotic action as opposed to  S. cerevisiae . They reveal for the first time the molecular-genetic basis of a probiotic action-related trait in  S. boulardii  and show that antibacterial potency of a probiotic microorganism can be due to strain-specific mutations within the same species. We suggest that acquisition of antibacterial activity through medium acidification offered a selective advantage to  S. boulardii  in its ecological niche and for its application as a probiotic.

genome research

Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast <i>Saccharomyces cerevisiae</i> var. <i>boulardii</i>

Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast Saccharomyces cerevisiae var. boulardii