Abstract

Regulation of the pap operon in uropathogenic Escherichia coli is phase variable. This phase variation arises from competition between regulatory proteins at two sites within the regulatory region, GATCdist and GATCprox. We have used the available literature data to design a stochastic model of the molecular interactions of pap regulation and expression during growth in a non-glucose environment at 37jC. The resulting wild-type model is consistent with reported data. The wild-type model served as a basis for two ‘‘in silico’’ mutant models for investigating the role of key regulatory components, the GATCdist binding site and the PapI interaction with Lrp at the GATCprox site. Our results show that competition at GATCdist is required for phase variation, as previously reported. However, our results suggest that removal of competition at GATCdist does not affect initial state dependence. Additionally, the PapI involvement in Lrp translocation from GATCprox to GATCdist is required for the initial state dependence but not for phase variation. Our results also predict that pap expression is maximized at low growth rates and minimized at high growth rates. These predictions provide a basis for further experimental investigation.