A Whole-cell Model to Simulate Mercuric Ion Reduction byE. coli under Stationary and Perturbed Conditions

Gram-negative bacteria display mercury resistance conferred by the plasmid encoded mer operon. A genetic regulatory circuit (GRC), inducible by the presence of mercury compounds in the environment, allows controlling the expression of at least 6-7 mer genes producing enzymes responsible for the mercuric ions transport and reduction. In spite of extensive studies on bacterial toxic metal resistance, few and rather unstructured kinetic models have been proposed to characterize the process dynamics. This paper aims at proposing an extended dynamic model, of modular construction, to reproduce the characteristics of GRC controlling the mercury uptake and reduction process. The illustrated case study uses experimental data from literature collected on cultures of E. coli cells cloned with the plasmid R100 to increase the source of mer operon. The available information is used to fit the model parameters and to adjust the GRC properties. The pathway includes seven regulatory modules placed in an E. coli growing cell on which response to external perturbations is studied. The model, accounting for the variable cell volume under isotonic conditions, can reproduce the GRC dynamic control in connection with the cell content replication, and various cell behaviours such as mer gene expression amplification at low levels of external stimuli, or cell content ‘ballast’ effect when coping with stationary or dynamic perturbations.