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1. A sequential decision making model of bacterial growth via quorum sensing

   https://doi.org/10.1109/ACSSC.2018.8645325  

   Vasconcelos, Marcos M.; Camar, Odilon; Mitra, Urbashi; Boedicker, James (October 2018, Proceedings of the Asilomar Conference on Signals, Systems, and Computers)

   Quorum sensing is a mechanism used by bacteria to coordinate the expression of certain exofactors which are more beneficial at higher cell densities. It has been argued that quorum sensing is a way for bacteria to control gene expression where some performance metric is being optimized. Herein, bacterial growth via quorum sensing is studied under the lens of optimal control theory. Under the assumption of perfect state observation, it is shown that quorum sensing is an optimal control strategy for an infinite horizon discounted reward function. 

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2. Quorum Sensing Regulators AphA and OpaR Control Expression of the Operon Responsible for Biosynthesis of the Compatible Solute Ectoine

   https://doi.org/10.1128/AEM.01543-19  

   Gregory, Gwendolyn J.; Morreale, Daniel P.; Carpenter, Megan R.; Kalburge, Sai S.; Boyd, E. Fidelma; Stabb, Eric V. (November 2019, Applied and Environmental Microbiology)

   ABSTRACT To maintain the turgor pressure of the cell under high osmolarity, bacteria accumulate small organic compounds called compatible solutes, either through uptake or biosynthesis. Vibrio parahaemolyticus , a marine halophile and an important human and shellfish pathogen, has to adapt to abiotic stresses such as changing salinity. Vibrio parahaemolyticus contains multiple compatible solute biosynthesis and transporter systems, including the ectABC-asp_ect operon required for de novo ectoine biosynthesis. Ectoine biosynthesis genes are present in many halotolerant bacteria; however, little is known about the mechanism of regulation. We investigated the role of the quorum sensing master regulators OpaR and AphA in ect gene regulation. In an opaR deletion mutant, transcriptional reporter assays demonstrated that ect expression was induced. In an electrophoretic mobility shift assay, we showed that purified OpaR bound to the ect regulatory region indicating direct regulation by OpaR. In an aphA deletion mutant, expression of the ect genes was repressed, and purified AphA bound upstream of the ect genes. These data indicate that AphA is a direct positive regulator. CosR, a Mar-type regulator known to repress ect expression in V. cholerae , was found to repress ect expression in V. parahaemolyticus . In addition, we identified a feed-forward loop in which OpaR is a direct activator of cosR , while AphA is an indirect activator of cosR . Regulation of the ectoine biosynthesis pathway via this feed-forward loop allows for precise control of ectoine biosynthesis genes throughout the growth cycle to maximize fitness. IMPORTANCE Accumulation of compatible solutes within the cell allows bacteria to maintain intracellular turgor pressure and prevent water efflux. De novo ectoine production is widespread among bacteria, and the ect operon encoding the biosynthetic enzymes is induced by increased salinity. Here, we demonstrate that the quorum sensing regulators AphA and OpaR integrate with the osmotic stress response pathway to control transcription of ectoine biosynthesis genes in V. parahaemolyticus . We uncovered a feed-forward loop wherein quorum sensing regulators also control transcription of cosR , which encodes a negative regulator of the ect operon. Moreover, our data suggest that this mechanism may be widespread in Vibrio species. 

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3. Parameters, architecture and emergent properties of the Pseudomonas aeruginosa LasI/LasR quorum-sensing circuit

   https://doi.org/10.1098/rsif.2022.0825  

   Schuster, Martin; Li, Christina; Smith, Parker; Kuttler, Christina (March 2023, Journal of The Royal Society Interface)

   Quorum sensing is a widespread process in bacteria that controls collective behaviours in response to cell density. Populations of cells coordinate gene expression through the perception of self-produced chemical signals. Although this process is well-characterized genetically and biochemically, quantitative information about network properties, including induction dynamics and steady-state behaviour, is scarce. Here we integrate experiments with mathematical modelling to quantitatively analyse the LasI/LasR quorum sensing pathway in the opportunistic pathogen Pseudomonas aeruginosa . We determine key kinetic parameters of the pathway and, using the parametrized model, show that quorum sensing behaves as a bistable hysteretic switch, with stable on and off states. We investigate the significance of feedback architecture and find that positive feedback on signal production is critical for induction dynamics and bistability, whereas positive feedback on receptor expression and negative feedback on signal production play a minor role. Taken together, our data-based modelling approach reveals fundamental and emergent properties of a bacterial quorum sensing circuit, and provides evidence that native quorum sensing can indeed function as the gene expression switch it is commonly perceived to be. 

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4. Synergy between c-di-GMP and Quorum-Sensing Signaling in Vibrio cholerae Biofilm Morphogenesis

   https://doi.org/10.1128/jb.00249-22  

   Prentice, Jojo A.; Bridges, Andrew A.; Bassler, Bonnie L. (January 2022, Journal of Bacteriology)

   O’Toole, George (Ed.)

   ABSTRACT Transitions between individual and communal lifestyles allow bacteria to adapt to changing environments. Bacteria must integrate information encoded in multiple sensory cues to appropriately undertake these transitions. Here, we investigate how two prevalent sensory inputs converge on biofilm morphogenesis: quorum sensing, which endows bacteria with the ability to communicate and coordinate group behaviors, and second messenger c-di-GMP signaling, which allows bacteria to detect and respond to environmental stimuli. We use Vibrio cholerae as our model system, the autoinducer AI-2 to modulate quorum sensing, and the polyamine norspermidine to modulate NspS-MbaA-mediated c-di-GMP production. Individually, AI-2 and norspermidine drive opposing biofilm phenotypes, with AI-2 repressing and norspermidine inducing biofilm formation. Surprisingly, however, when AI-2 and norspermidine are simultaneously detected, they act synergistically to increase biofilm biomass and biofilm cell density. We show that this effect is caused by quorum-sensing-mediated activation of nspS - mbaA expression, which increases the levels of NspS and MbaA, and in turn, c-di-GMP biosynthesis, in response to norspermidine. Increased MbaA-synthesized c-di-GMP activates the VpsR transcription factor, driving elevated expression of genes encoding key biofilm matrix components. Thus, in the context of biofilm morphogenesis in V. cholerae, quorum-sensing regulation of c-di-GMP-metabolizing receptor levels connects changes in cell population density to detection of environmental stimuli. IMPORTANCE The development of multicellular communities, known as biofilms, facilitates beneficial functions of gut microbiome bacteria and makes bacterial pathogens recalcitrant to treatment. Understanding how bacteria regulate the biofilm life cycle is fundamental to biofilm control in industrial processes and in medicine. Here, we demonstrate how two major sensory inputs—quorum-sensing communication and second messenger c-di-GMP signaling—jointly regulate biofilm morphogenesis in the global pathogen Vibrio cholerae. We characterize the mechanism underlying a surprising synergy between quorum-sensing and c-di-GMP signaling in controlling biofilm development. Thus, the work connects changes in cell population density to detection of environmental stimuli in a pathogen of clinical significance. 

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5. Microbial Primer: LuxR-LuxI Quorum Sensing: This article is part of the Microbial Primer collection.

   https://doi.org/10.1099/mic.0.001343  

   Soto-Aceves, Martin P; Diggle, Stephen P; Greenberg, E Peter (September 2023, Microbiology)

   Quorum sensing is a term describing bacterial cell-to-cell communication systems for monitoring and responding to changes in population density. This primer serves as an introduction to the canonical LuxR-LuxI-type quorum sensing circuits common to many species of Gram-negative bacteria. Quorum sensing can synchronize behaviours across a community. Different species employ quorum sensing strategies to control specific behaviours such as bioluminescence, virulence factor production, secondary metabolite production, and biofilm formation. 

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