title: Antagonistic autoregulation speeds up a homogeneous response in Escherichia coli.
abstract: By integrating positive and negative feedback loops, biological systems establish intricate gene expression patterns linked to multistability, pulsing, and oscillations. This depends on the specific characteristics of each interlinked feedback, and thus one would expect additional expression programs to be found. Here, we investigate one such program associated with an antagonistic positive and negative transcriptional autoregulatory motif derived from the multiple antibiotic resistance (mar) system of Escherichia coli. We studied the dynamics of the system by combining a predictive mathematical model with high-resolution experimental measures of the response both at the population and single-cell level. We show that in this motif the weak positive autoregulation does not slow down but rather enhances response speedup in combination with a strong negative feedback loop. This balance of feedback strengths anticipates a homogeneous population phenotype, which we corroborate experimentally. Theoretical analysis also emphasized the specific molecular properties that determine the dynamics of the mar phenotype. More broadly, response acceleration could provide a rationale for the presence of weak positive feedbacks in other biological scenarios exhibiting these interlinked regulatory architectures.
authors: Instituto de Biología Molecular y Cellular de Plantas, CSIC-UPV, 46022 Valencia, Spain.
authors: Guillermo
authors: G
authors: Rodrigo
authors: Logic of Genomic Systems Laboratory, CNB-CSIC, 28049 Madrid, Spain.
authors: Djordje
authors: D
authors: Bajic
authors: Logic of Genomic Systems Laboratory, CNB-CSIC, 28049 Madrid, Spain.
authors: Ignacio
authors: I
authors: Elola
authors: Logic of Genomic Systems Laboratory, CNB-CSIC, 28049 Madrid, Spain.
authors: Juan F
authors: JF
authors: Poyatos
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008962:Models, Theoretical; D012097:Repressor Proteins / Q000378:metabolism; D012459:Salicylates / Q000633:toxicity
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C080002:MarA protein, E coli; C080004:MarR protein, E coli; D012097:Repressor Proteins; D012459:Salicylates