Multicellularity and virulence in the budding yeast, Saccharomyces cerevisiae

In the real world, microbes must cope with environmental fluctuations, compete for scarce resources, and avoid predation. One adaptation to survive this tangled web is the formation of multicellular aggregates, such as biofilms, which are known to be associated with pathogenicity. Despite the importance of the yeast Saccharomyces cerevisiae to biomedical research, little is known about the natural variation in its multicellular, biofilm-related traits. We investigated five multicellular phenotypes in a diverse, worldwide panel of ∼1000 isolates. We found that all traits varied significantly and ∼2/3 of the isolates expressed at least one multicellular trait. Both recent ecology and evolutionary history explained some of this variation, with clinical isolates exhibiting increased levels of three biofilm-related traits. When tested against wax moth larvae, hyper-multicellular isolates tended to be more virulent than non-multicellular isolates. Genome-wide association analysis on each trait suggested a genetic architecture of many small effect loci, compatible with polygenic adaptation. Only four genes, SLN1 , ECM5 , MLP2 , and ECM9 , were shared among the traits; deletion of MLP2 and ECM9 verified their association with multicellularity. Our results show that this yeast expresses far more multicellularity than previously appreciated and suggest that the aggregative phenotypes are likely evolving independently.