A bacterial growth law out of steady-state

Abstract

SummaryBacterial growth depends on numerous reactions, and yet follows surprisingly simple laws that inspired biologists for decades. Growth laws until now primarily dealt with steady-state exponential growth in constant conditions. However, bacteria in nature often face fluctuating environments, with nutritional upshifts and downshifts. We therefore ask whether there are growth laws that apply to changing environments. We derive a law for strong upshifts using an optimal resource-allocation model that was previously calibrated at steady-state growth: the post-shift growth rate equals the geometrical mean of the pre-shift growth rate and the growth rate on saturating carbon. We test this using chemostat and robotic batch culture experiments, as well as previous data from several species, and find good agreement with the model predictions. The increase in growth rate after an upshift indicates that ribosomes have spare capacity. We demonstrate theoretically that spare ribosomal capacity has the cost of slow steady-state growth, but is beneficial in fluctuating environments because it prevents large overshoots in intracellular metabolites after an upshift and allows rapid response to change. We also provide predictions for downshifts for future experimental tests. Spare capacity appears in diverse biological systems, and the present study quantifies the optimal degree of spare capacity, which rises the slower the growth rate, and suggests that it can be precisely regulated.

Time-series genome-centric analysis unveils bacterial response to operational disturbance in activated sludge

“…Yet we observed differences at the genomic level that are consistent with recently proposed models, which predict that competitive advantage of bacteria under changing environmental condition is achieved by reserve capacity of ribosomes and transporters. Accordingly, sub-saturation allows bacteria to rapidly adapt in fluctuating environments by producing new ribosomes and high affinity transporters for optimal growth (54,55). We also observed that the disturbed period was significantly enriched in secretion system, which are used to deliver a variety of different proteins, including bacterial toxins and degradative enzymes such as proteases and lipases (56).…”

(p)ppGpp directly regulates translation initiation during entry into quiescence

“…However, recent work suggests that ribosomes are actually in excess, and that only a fraction are active, especially under non-exponential growth (Dai et al, 2016; Li et al, 2018). This excess would be particularly useful for the exit from quiescence, since the ability to transition to maximal protein synthesis as quickly as possible would provide a clear selective advantage (Korem Kohanim et al, 2018; Remigi et al, 2019). From this perspective, a reversible process such as the competitive binding of an inhibitor such as (p)ppGpp to a translational GTPase would facilitate the necessary down-regulation of protein synthesis to minimize energy consumption without impairing an optimal response to growth-permissive conditions.…”

Ribosome dimerization prevents loss of essential ribosomal proteins during quiescence

“…Given that ribosome synthesis is the single most energy consuming process in cells, preventing ribosome degradation, even when protein synthesis levels are low, would be evolutionarily favorable (6). In addition, a readily available, excess store of ribosomes under nutrient limitation would facilitate rapid resumption of growth when nutrients become available (43). The ability to transition to maximal protein synthesis as quickly as possible imparts a clear selective advantage for cells with higher ribosomal content (44, 45).…”