Mapping Gene-Microbe Interactions: Insights from Functional Genomics Co-culture Experiments between Saccharomyces cerevisiae and Pseudomonas spp.

Microbial interactions contribute to shape ecosystems and their functions. The interplay between microorganisms also shapes the evolutionary trajectory of each species, by imposing metabolic and physiological selective pressures. The mechanisms underlying these interactions are thus of interest to improve our understanding of microbial evolution at the genetic level. Here we applied a functional genomics approach in the model yeast Saccharomyces cerevisiae to identify the fitness determinants of naive biotic interactions. We used a barcoded prototroph yeast deletion collection to perform pooled fitness competitions in co-culture with seven Pseudomonas spp natural isolates. We found that co-culture had a positive impact on fitness profiles, as in general the deleterious effects of loss of function in our nutrient-poor media were mitigated. In total, 643 genes showed a fitness difference in co-culture, most of which can be explained by a media diversification procured by bacterial metabolism. However, a large fraction (36%) of gene-microbe interactions could not be recaptured in cell-free supernatant experiments, showcasing that feedback mechanisms or physical contacts modulate these interactions. Also, the gene list of some co-cultures was enriched with homologs in other eukaryote species, suggesting a variable degree of specificity underlying the mechanisms of biotic interactions and that these interactions could also exist in other organisms. Our results illustrate how microbial interactions can contribute to shape the interplay between genomes and species interactions, and that S. cerevisiae is a powerful model to study the impact of biotic interactions.