Fundamental Limits on the Rate of Bacterial Growth and Their Influence on Proteomic Composition

Nathan Belliveau*, Griffin Chure*, Christina L. Hueschen, Hernan G. Garcia, Jane Kondev, Julie Theriot, Rob Phillips
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† Selected as the cover article for the September 2021 issue of Cell Systems.

Non-expert Summary

The behavior of cells is predominantly guided by the set of genes that are active, meaning they are being used (in most cases) to make proteins. While an organism like a bacterium may have several thousand genes, not all of them are being used at once, and the ones that are used are typically used in different amounts in different environmental conditions. While many careful measurements of how many proteins each gene is making have been made in well-studied organisms like the bacterium E. coli, we remain largely ignorant of why the different proteins are made at different levels. In this paper, we use very simple mathematics to make an order-of-magnitude estimate of how many proteins would be needed for many of the major processes cells have to undertake. We see if these estimates are reasonable by comparing them to measurements, revealing that in almost all cases that they are accurate. We then use these estimates to arrive at the conclusion that the proteins needed to make other proteins imposes a strict speed limit on how fast cells can grow, and their abundances can be used to predict this speed.

Scientific Abstract

Despite abundant measurements of bacterial growth rate, cell size, and protein content, we lack a rigorous understanding of what sets the scale of these quantities and when protein abundances should (or should not) depend on growth rate. Here, we estimate the basic requirements and physical constraints on steady-state growth by considering key processes in cellular physiology across a collection of Escherichia coli proteomic data covering ≈ 4,000 proteins and 36 growth rates. Our analysis suggests that cells are predominantly tuned for the task of cell doubling across a continuum of growth rates; specific processes do not limit growth rate or dictate cell size. We present a model of proteomic regulation as a function of nutrient supply that reconciles observed interdependences between protein synthesis, cell size, and growth rate and propose that a theoretical inability to parallelize ribosomal synthesis places a firm limit on the achievable growth rate.