 Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social TraitKerry E Boyle, Hilary Monaco, Dave van Ditmarsch, Maxime Deforet and Joao B Xavier PLOS Computational Biology, 2015, vol. 11, issue 6, 1-26 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.Author Summary: Although bacteria are not multicellular organisms, they commonly live in large communities and engage in many cooperative behaviors. Cooperation can allow bacteria to access additional nutrients, but it requires the secretion of products that will be shared by the community. How bacteria make the molecular decision to cooperate within a community is still not completely understood. The bacterium Pseudomonas aeruginosa regulates the secretion of one of these shared products, rhamnolipids, using information about population density and nutrient availability in its environment. Expression of the operon rhlAB is required for the bacteria to produce rhamnolipids. We use a combined computational and experimental approach to investigate how P. aeruginosa continually combines current information of population density and nutrient availability to determine if it should express rhlAB. We find that when conditions are nutrient rich, P. aeruginosa uses population density to modulate the amount rhlAB expression, however when the bacteria are starved for nutrients the starvation condition largely determines how the bacteria will express rhlAB. Because the bacteria continually adjust expression based on the current conditions, the molecular decision to produce rhamnolipids can be adjusted if either population density or nutrient conditions change. Our combined computational and experimental approach sheds new light on the rich regulatory dynamics that govern a cellular decision to cooperate. Date: 2015 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1004279 DOI: 10.1371/journal.pcbi.1004279 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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