The development of a model of a bacterial phosphorelay signal transduction system

The BvgAS two-component system controls virulence in the human respiratory pathogen Bordetella pertussis, the etiological agent of whooping cough. BvgAS is unlike orthodox two-component signal transduction systems in that it employs a four step phosphorelay from the sensor protein BvgS to the response regulator BvgA, instead of the more common two step phosphotransfer. Further, B. pertussis displays at least three distinct phenotypic phases, each characterized by maximal expression of some genes and minimal expression of others. In vitro experiments are modeled by ordinary differential equations of chemical kinetics in order to obtain kinetic parameter estimates. Completed versions of the model are then simulated using deterministic (ODE), stochastic (Gillespie's algorithm) or multiscale (tau leaping, slow-scale SSA or hybrid) chemical kinetics algorithms, depending on what is appropriate. Preliminary results indicate that the full complexity of the three phenotypic phases of B. pertussis cannot be achieved without incorporating the phosphorelay (i.e. by simple two-step phosphotransfer) or BvgAS autoregulation in the model