Deconstructing a multiple antibiotic resistance regulation through the quantification of its input function

Inferring the regulatory complexity of the mar operon though the characterization of the input function. a A complex regulatory scheme can be associated to a particular input function (left) whose change when a regulator is perturbed helps us appreciate the role of this regulator (right). b Scheme of the mar core control network, which includes the components of the mar operon, MarR (a repressor acting as a dimer), MarA (an activator acting as a monomer), and MarB (a periplasmatic protein that may act as repressor), as well as two additional elements that are not part of the operon, CRP:cAMP and Rob (both monomeric activators). The mar operon (through MarA) controls the bacterial response to a number of toxic compounds, including antibiotics, and is also sensitive to metabolic signals (through CRP). Dashed lines indicate weak regulations. Inset illustrates the logical regulatory architecture of the operon. c Input function (promoter activity in steady state as a function of salicylate) measured by means of a YFP reporter system (YFP follows the dynamics of MarR30). Functions corresponding to the wild type and several mutant strains are shown. Open circles correspond to experimental data (error bars are standard deviations of three replicates); solid lines correspond to model predictions of gene expression levels (MarR, representation in arbitrary units, AU