Acyl-homoserine lactone (AHL)-mediated quorum sensing (QS) controls the production of numerous intra-and extracellular products across many species of Proteobacteria. Although these cooperative activities are often costly at an individual level, they provide significant benefits to the group. Other potential roles for QS include the restriction of nutrient acquisition and maintenance of metabolic homeostasis of individual cells in a crowded but cooperative population. Under crowded conditions, QS may function to modulate and coordinate nutrient utilization and the homeostatic primary metabolism of individual cells. Here, we show that QS down-regulates glucose uptake, substrate level and oxidative phosphorylation, and de novo nucleotide biosynthesis via the activity of the QS-dependent transcriptional regulator QsmR (quorum sensing master regulator R) in the rice pathogen Burkholderia glumae. Systematic analysis of glucose uptake and core primary metabolite levels showed that QS deficiency perturbed nutrient acquisition, and energy and nucleotide metabolism, of individuals within the group. The QS mutants grew more rapidly than the wild type at the early exponential stage and outcompeted wild-type cells in coculture. Metabolic slowing of individuals in a QS-dependent manner indicates that QS acts as a metabolic brake on individuals when cells begin to mass, implying a mechanism by which AHL-mediated QS might have evolved to ensure homeostasis of the primary metabolism of individuals under crowded conditions. A cyl-homoserine lactone (AHL)-mediated quorum sensing (QS) controls diverse behaviors, including virulence, biofilm formation, and motility, in many Proteobacteria (1-3). Such QSdependent activities are the result of density-dependent expression of both intra-and extracellular gene products important for survival in crowded conditions (4-7). Other roles for bacterial QS have been proposed, including allowing bacteria to control nutrient uptake and maintain individual metabolic homeostasis within a crowded but cooperative population. The metabolic status of bacteria is usually defined as the average metabolic activity of individual cells in a population; however, the concepts of population biology have often been ignored in this context.Little is known regarding whether or not individual cells change their primary metabolism under crowded, but cooperative, conditions or how they maintain metabolic homeostasis at the population level. In addition to the feedback inhibition circuits characteristic of many biochemical processes (8-10), we hypothesized that QS might control both glucose uptake and metabolic homeostasis of individual cells in crowded populations based upon earlier analyses of QS-dependent gene expression in Burkholderia glumae and the role of QS in regulating the respiration of Burkholderia thailandensis (11,12). The model organism used in this study, B. glumae, is an important agricultural pathogen due to its ability to cause rice panicle blight. Compared with other closely related pathogenic bac...