title: Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait.
abstract: Many unicellular organisms live in multicellular communities that rely on cooperation between cells. However, cooperative traits are vulnerable to exploitation by non-cooperators (cheaters). 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 cooperative rhamnolipids required for swarming in Pseudomonas aeruginosa. We combine mathematical 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 dependent 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-driven activation that integrates metabolic prudence with quorum sensing in a non-digital manner and allows P. aeruginosa cells to invest in cooperation only when the population size is large enough (quorum sensing) and individual cells have enough metabolic resources to do so (metabolic prudence). Thus, the quantitative description of rhlAB regulatory dynamics brings a greater understating to the regulation required to make swarming cooperation stable.
authors.affiliation: Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, New York, United States of America; Program in Computational Biology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Boyle
authors.affiliation: Program in Computational Biology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Tri-Institutional Training Program in Computational Biology and Medicine, New York, New York, United States of America.
authors.forename: Hilary
authors.initials: H
authors.lastname: Monaco
authors.affiliation: Program in Computational Biology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Dave
authors.initials: D
authors.lastname: van Ditmarsch
authors.affiliation: Program in Computational Biology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Maxime
authors.initials: M
authors.lastname: Deforet
authors.affiliation: Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, New York, United States of America; Program in Computational Biology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Tri-Institutional Training Program in Computational Biology and Medicine, New York, New York, United States of America.
authors.forename: Joao B
authors.initials: JB
authors.lastname: Xavier
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000378:metabolism; D018533:Biomass; D005502:Food; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D049452:Green Fluorescent Proteins / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D053858:Metabolic Networks and Pathways; D008856:Microscopy, Fluorescence; D008962:Models, Theoretical; D009584:Nitrogen / Q000737:chemistry; D009876:Operon; D011401:Promoter Regions, Genetic; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D053038:Quorum Sensing; D012984:Software
chemical_list: D001426:Bacterial Proteins; D008055:Lipids; D049452:Green Fluorescent Proteins; D007501:Iron; D009584:Nitrogen