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Based on the phosphorelay kinetics operative within BvgAS two componentsystem we propose a mathematical framework for signal transduction and generegulation of phenotypic phases in Bordetella pertussis. The proposed modelidentifies a novel mechanism of transcriptional interference between twopromoters present in the bvg locus. To understand the system behavior underelevated temperature, the developed model has been studied in two differentways. First, a quasi-steady state analysis has been carried out for the twocomponent system, comprising of sensor BvgS and response regulator BvgA. Thequasi-steady state analysis reveals temperature induced sharp molecular switch,leading to amplification in the output of BvgA. Accumulation of a large pool ofBvgA thus results into differential regulation of the downstream genes,including the gene encoding toxin. Numerical integration of the full networkkinetics is then carried out to explore time dependent behavior of differentsystem components, that qualitatively capture the essential features ofexperimental results performed in vivo. Furthermore, the developed model hasbeen utilized to study mutants that are impaired in their ability tophosphorylate the transcription factor, BvgA, of the signaling network.

Positive feedback and temperature mediated molecular switch controls differential gene regulation in Bordetella pertussis