Quorum sensing (QS) explains a type of bacterial cell-cell communication mediated by exocellular compounds that act as autoinducers (AIs). As such, QS can be considered the most primordial form of language. QS has profound implications for the control of many important traits (e.g.biofilm formation, secretion of virulence factors, etc.). Conceptually, the QS response can be split into its “listening” and “speaking” components,i.e.the power to sense AI levelsvs.the ability to synthesize and release these molecules. By explaining the cell-density dependence of QS behavior as the consequence of the system’s arrival to a threshold AI concentration, models of QS have traditionally assumed a salient role for the “QS speaking” module during bacterial cell-to-cell communication. In this paper, we have provided evidence that challenges this AI-centered view of QS and establishes LuxR-like activators at the center of QS. Our observation that highly coordinated, cell-density dependent responses can occur in the absence of AI production, implies that the ability to launch such responses is engrained within the “QS listening” module. Our data indicates that once a critical threshold of intracellular activator monomers in complex with AI is reached, a highly orchestrated QS response ensues. While displaying a clear cell-density dependence, such response does not strictly require the sensing of population levels by individual cells. We additionally show, bothin vivoandin silico, that despite their synchronous nature, QS responses do not require that all the cells in the population participate in the response. Central to our analysis was the discovery that percolation theory (PT) can be used to mathematically describe QS responses. While groundbreaking, our results are in agreement with and integrate the latest conclusions reached in the field. We explain for the first time, the cell-density-dependent synchronicity of QS responses as the function of a single protein, the LuxR-like activator, capable of coordinating the temporal response of a population of cells in the absence of cell-to-cell communication. Being QS the most primordial form of speech, our results have important implications for the evolution of language in its ancient chemical form.Abbreviations3Dthree dimensionalacwthreshold intracellular concentration of activator moleculesAHLacyl-homoserine lactoneAHLfischN-(3-oxohexanoyl)-L-homoserine lactoneAHLviolN-hexanoyl-DL-homoserine-lactoneAIautoinducera.uarbitrary unitsBMBbromophenol blueCAtrans-cinnamaldehydeFlfluorescence intensityFI/OD600density-normalized fluorescence intensityGFPgreen fluorescent proteinMwmolecular weightPTpercolation theoryQSquorum sensingtcpercolation critical timewtwild type
Covalently and ionically, dually crosslinked chitosan nanoparticles block quorum sensing and affect bacterial cell growth on a cell-density dependent manner