Optimality and sub-optimality in a bacterial growth law

Abstract

Organisms adjust their gene expression to improve fitness in diverse environments. But finding the optimal expression in each environment presents a challenge. We ask how good cells are at finding such optima by studying the control of carbon catabolism genes in Escherichia coli. Bacteria show a growth law: growth rate on different carbon sources declines linearly with the steady-state expression of carbon catabolic genes. We experimentally modulate gene expression to ask if this growth law always maximizes growth rate, as has been suggested by theory. We find that the growth law is optimal in many conditions, including a range of perturbations to lactose uptake, but provides sub-optimal growth on several other carbon sources. Combining theory and experiment, we genetically re-engineer E. coli to make sub-optimal conditions into optimal ones and vice versa. We conclude that the carbon growth law is not always optimal, but represents a practical heuristic that often works but sometimes fails.

Synthesis and degradation of FtsZ quantitatively predict the first cell division in starved bacteria

“…Furthermore, measured central carbon metabolite pools recrudesce and deplete within seconds, meaning even minuscule glucose passes through quickly. The limitation for division occurred on the protein level and not a specific metabolite, echoing recent work that argues the protein production and not metabolic activity limits cell cycle progression (Erickson et al , ; Towbin et al , ).…”

Escherichia coli translation strategies differ across carbon, nitrogen and phosphorus limitation conditions

“…Our macroscopic ribosome dynamics model highlights how cells can tune total ribosome number, the fraction of working ribosomes and the rate of translational elongation to achieve the same total protein production rate while balancing other constraints such as reduced amino acid availability or the need to rapidly accelerate growth. This strategy could help explain recent reports of the suboptimality of protein allocation for E. coli in the presence of poor carbon sources 43–46 , the suboptimal expression levels of essential genes in Bacillus subtilis 47 and excess ribosome production in S. cerevisiae 48,49 . Future studies will address the consequences of adaptation strategies in dynamic conditions, for example the generality of optimizing growth rate transitions at the expense of steady-state growth.…”

An analytical theory of balanced cellular growth

“…For non-interacting unicellular organisms in constant environments, the rate of this self-replication is equivalent to their evolutionary fitness 1 : fast-growing cells outcompete those growing more slowly. Accordingly, we expect that natural selection favoring fast growth in specific environments has played an important role in shaping the physiology of many microbial organisms 2,3 .…”

“…Cellular growth has to be balanced over the cell cycle, i.e., all cellular components must be reproduced in proportion to their abundances 4 . Casting these constraints into a mathematical model and characterizing states of optimal growth may provide a detailed understanding of central aspects of bacterial physiology 3,[5][6][7][8] .…”