Co-regulation of cooperative and private traits by PsdR in Pseudomonas aeruginosa

Social interactions profoundly shape the dynamics and functionality of microbial populations. However, mechanisms governing the regulation of cooperative or individual traits have remained elusive. Here, we investigated the regulatory mechanisms of social behaviors by characterizing the fitness of transcriptional regulator PsdR mutants in cooperating Pseudomonas aeruginosa populations. In a canonical model described previously, PsdR was shown to solely have a nonsocial role in adaptation of these populations by controlling the intracellular uptake and processing of dipeptides. In addition to these known private traits, we found that PsdR mutants also enhanced cooperation by increasing the production of quorum sensing (QS)-regulated public goods. Although private dipeptide utilization promotes individual absolute fitness, it only partially accounts for the growth advantage of PsdR mutants. The absence of the QS master regulator LasR delayed the appearance of PsdR variants in an evolution experiment. We also demonstrated that the growth fitness of PsdR mutants is determined by a combination of the QS-mediated cooperative trait and the dipeptide metabolism-related private trait. This dual trait is co-regulated by PsdR, leading to the rapid spread of PsdR variants throughout the population. In conclusion, we identified a new social model of co-regulating cooperative and private traits in PsdR variants, uncovering the social and nonsocial roles of this transcriptional regulator in cooperating bacterial populations. Our findings advance the fundamental understanding of bacterial social interactions and provide insights into population evolution, pathogen infection control and synthetic biotechnology.