Effect of Polyphosphate Metabolism on the Escherichia coli Phosphate-Starvation Response

Abstract

A previously developed dynamic model of the Escherichia coli Pho regulon was extended to investigate the effect of polyphosphate synthesis and degradation on this control system. Differential equations for ATP and polyphosphate were formulated, and the model was applied to the growth of cells containing the ppk and ppx genes under control of separate, inducible promoters. In agreement with recent experimental observations, the degradation of polyphosphate by PPX during a period of phosphate limitation could repress the phosphate-starvation response. This is attributed to the release of phosphate from the cell into the periplasm, where it can be detected by the external phosphate sensor. A segregated model was then developed to account for differences in K(I), the dissociation constant for the repression complex, among cells of the population. Since K(I) is the key parameter in determining whether the Pho response is induced or repressed at a particular surface phosphate concentration, this permitted the induction of some cells while others remained repressed. The induction profiles resulting from the population-averaged values more closely matched experimental results than did those with the nonsegregated model.

Quantitative Analysis of Bacterial Gene Expression by Using the gusA Reporter Gene System

“…When validated, the model can be used to predict in silico the effects of external signals on expression of the gene studied under nonexperimentally tested conditions. The use of mathematical models based on differential equations to describe and predict the behavior of cellular processes is becoming widespread (4,6,8,9,13,20,27). According to previous studies with E. coli, a steady state can be achieved within 5 reactor residence times (12,23,24), which equals 33 h at a dilution rate of 0.15 h Zhulin et al (30) and coincided with generation of a maximal proton motive force.…”

Modeling Metabolic Networks for Mammalian Cell Systems: General Considerations, Modeling Strategies, and Available Tools

“…This model integrates a large amount of biological information regarding this system and it was applied to the overexpression of heterologous genes. A structured extension of this model was also developed, incorporating differences in gene regulation among cells of the population and the heterogeneity of their response, as well as ATP synthesis and utilization [105]. This is a good example of the capability of detailed kinetic models to explore the dynamic response of cellular and metabolic processes.…”

Mathematical Modeling of Genetic Regulatory Networks: Stress Responses inEscherichia coli

“…14,129-133). However, differential equation models have also been used to model the response of E. coli to other stresses, such as the response to a heat shock [96], bacteriophage infection [6,134,135], phosphate starvation [136], or the SOS response [103,136].…”