Bacterial gene regulation in diauxic and nondiauxic growth

Biology – Quantitative Biology – Molecular Networks

Scientific paper

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Accepted, J Theoret Biol (47 pages)

Scientific paper

When bacteria are grown on a mixture of two growth-limiting substrates, they exhibit a rich spectrum of substrate consumption patterns including diauxic growth, simultaneous consumption, and bistable growth. In previous work, we showed that a minimal model accounting only for enzyme induction and dilution captures all the substrate consumption patterns. Here, we construct the bifurcation diagram of the minimal model. The bifurcation diagram explains several general properties of mixed-substrate growth. (1) In almost all cases of diauxic growth, the "preferred" substrate is the one that, by itself, supports a higher specific growth rate. In the literature, this property is often attributed to optimality of regulatory mechanisms. Here, we show that the minimal model, which contains only induction, displays the property under fairly general conditions. This suggests that the higher growth rate of the preferred substrate is an intrinsic property of the induction and dilution kinetics.(2) The model explains the phenotypes of various mutants containing lesions in the regions encoding for the operator, repressor, and peripheral enzymes. A particularly striking phenotype is the "reversal of the diauxie" in which the wild-type and mutant strains consume the very same two substrates in opposite order. This phenotype is difficult to explain in terms of molecular mechanisms, but it turns out to be a natural consequence of the model. We show furthermore that the model is robust. The key property of the model, namely, the competitive dynamics of the enzymes, is preserved even if the model is modified to account for various regulatory mechanisms. Finally, the model has important implications for size regulation in development, since it suggests that protein dilution is one mechanism for coupling patterning and growth.

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