Interspecies interactions drive bacterial proteome reorganization and emergent metabolism

Species in microbial communities need to stave off competition and capitalize on new resources that become available because of metabolic activities of others. However, intra-cellular molecular changes that underpin these responses are understudied, preventing mechanistic insights into community function and dynamics. Here we analyse proteomic and metabolomic responses in 104 pairwise co-cultures of 15 gut bacteria, spanning a diversity of ecological interactions from competition to mutualism. We find that molecular responses to co-culturing are substantial, with typically 50% of the quantified proteome changing in at least one co-culture, jointly influenced by genome size, species abundance and pH. Even closely related species and orthologue proteins show different expression profiles in response to the same partner, indicating functional diversification at both protein and species level. Small-molecule transport and carbon metabolism are among the most responsive processes, indicating pervasive metabolic interactions. Using metabolomics, we identify likely cross-fed metabolites, emergent polyamine metabolism and niche partitioning in amino acid utilization. Overall, our study uncovers how bacteria respond to the presence of other species through extensive remodelling of their proteome and metabolome.