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

The yeast 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 , which is generally used in classical food applications. They have an almost identical genome sequence, making the genetic basis of probiotic potency in puzzling. We now show that 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 and parent strains, we succeeded in mapping the underlying QTLs and identified mutant alleles of and as the causative alleles. Both genes contain a SNP unique to ( and ) and are fully responsible for its high acetic acid production. strains show different levels of acetic acid production, depending on the copy number of the allele. Our results offer the first molecular explanation as to why could exert probiotic action as opposed to They reveal for the first time the molecular-genetic basis of a probiotic action-related trait in 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 in its ecological niche and for its application as a probiotic.