RESEARCH ARTICLE Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait

Many unicellular organisms live in multicellular communities that rely on cooperation between cells. However, cooperative traits are vulnerable to exploitation by non-cooperators (cheat-ers). We expand our understanding of the molecular mechanisms that allow multicellular systems to remain robust in the face of cheating by dissecting the dynamic regulation of coop-erative rhamnolipids required for swarming in Pseudomonas aeruginosa. We combine mathe-matical modeling and experiments to quantitatively characterize the integration of metabolic and population density signals (quorum sensing) governing expression of the rhamnolipid synthesis operon rhlAB. The combined computational/experimental analysis reveals that when nutrients are abundant, rhlAB promoter activity increases gradually in a density depen-dent way. When growth slows down due to nutrient limitation, rhlAB promoter activity can stop abruptly, decrease gradually or even increase depending on whether the growth-limiting nutrient is the carbon source, nitrogen source or iron. Starvation by specific nutrients drives growth on intracellular nutrient pools as well as the qualitative rhlAB promoter response, which itself is modulated by quorum sensing. Our quantitative analysis suggests a supply