John Casey and Michael J. Follows (2020), A steady-state model of microbial acclimation to substrate limitation, PLoS Computational Biology, doi: 10.1371/journal.pcbi.1008140Summary:
The mechanics of resource-limited microbial growth is a fundamental focus in cell biology and biophysics. Physiological acclimation plays a key role in microbial growth rate dependence on the availability of a limiting resource, but progress has been mostly rooted in theoretical studies due to a lack of relevant experimental data. In light of new quantitative proteomics data that disagree with current models, we revisited the physics of substrate transport and propose a model, based on a different set of assumptions, which applies to the steady-state scenario. Depending on the design of the transport system, the proposed model predicts that microbial growth rate dependence on substrate availability can take on a familiar hyperbolic shape (e.g., Monod) or a piecewise linear shape, not unlike the Blackman kinetics model which fell out of favor long ago. The sharp transition appears from a discontinuity which marks a critical substrate concentration, above which physiological acclimation can sustain maximal growth rates, and below which diffusion is strictly limiting. We implemented the model in Escherichia coli using a combination of flux balance analysis, molecular modeling, and quantitative proteomics data. Predicted kinetics closely matched experimental observations across a range of carbon substrates, and the model can be easily implemented for other systems.