A steady-state model of microbial acclimation to substrate limitation.

John R Casey,Michael J Follows,William Cannon

doi:10.1371/journal.pcbi.1008140

Abstract

Microbes acclimate to changes in substrate availability by altering the number of transporters on the cell surface, however there is some disagreement on just how. We revisit the physics of substrate uptake and consider the steady-state scenario whereby cells have acclimated to maximize fitness. Flux balance analysis of a stoichiometric model of Escherichia coli was used in conjunction with quantitative proteomics data and molecular modeling of membrane transporters to reconcile these opposing views. An emergent feature of the proposed model is a critical substrate concentration S*, which delineates two rate limits. At concentrations above S*, transporter abundance can be regulated to maintain uptake rates as demanded by maximal growth rates, whereas below S*, uptake rates are strictly diffusion limited. In certain scenarios, the proposed model can take on a qualitatively different shape from the familiar hyperbolic kinetics curves, instead resembling the long-forgotten Blackman kinetics.

Highlights

Microbial growth rates may be limited by catalytic rates or by the rate of diffusion of resources, which are often supplied with some irregularity in the natural environment
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 which 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

Summary

Introduction

Microbial growth rates may be limited by catalytic rates or by the rate of diffusion of resources, which are often supplied with some irregularity in the natural environment. One view (“Model A”) predicts that, at very low substrate concentrations, the diffusive flux is low and very few transporters would be required to match uptake rates to encounter rates. Uptake rates become limited by the number of transporters, so more are synthesized [1,2,3,4,5,6,7,8]. Another view (“Model B”) predicts the opposite; at low substrate concentrations the encounter rate is limiting, so high transporter abundance is favored, while at higher concentrations resources are allocated for use elsewhere in the proteome [9,10,11,12,13]. Considering the evolution of these two divergent views, it is interesting that both evolved under different assumptions from the same underlying physics [14]

Methods

Results

Discussion

Conclusion