Plasticity of growth laws tunes resource allocation strategies in bacteria

Abstract

Bacteria like E. coli grow at vastly different rates on different substrates, however, the precise reason for this variability is poorly understood. Different growth rates have been attributed to nutrient quality, a key parameter in bacterial growth laws. However, it remains unclear to what extent nutrient quality is rooted in fundamental biochemical constraints like the energy content of nutrients, the protein cost required for their uptake and catabolism, or the capacity of the plasma membrane for nutrient transporters. Here, we show that while nutrient quality is indeed reflected in protein investment in substrate-specific transporters and enzymes, this is not a fundamental limitation on growth rate. We show that it is possible to turn mannose, one of the poorest substrates of E. coli, into one of the best substrates by reengineering chromosomal promoters of the mannose transporter and metabolic enzymes required for mannose degradation. However, we show that this faster growth rate comes at the cost of diverse cellular capabilities, reflected in longer lag phases, worse starvation survival and lower motility. We show that addition of cAMP to the medium can rescue these phenotypes but imposes a corresponding growth cost. Based on these data, we propose that nutrient quality is largely a self-determined, plastic property that can be modulated by the fraction of proteomic resources devoted to a specific substrate in the much larger proteome sector of catabolically activated genes. Rather than a fundamental biochemical limitation, nutrient quality reflects resource allocation decisions that are shaped by evolution in specific ecological niches and can be quickly adapted if necessary. Author summaryBacteria grow at very different rates on different substrates. Therefore, the substrates themselves are often denoted as rich substrates versus poor substrates, referring to their nutrient quality. Nutrient quality is also a key parameter in bacterial growth laws that determines substrate-specific growth rate. However, it remains unclear which properties make a specific carbon source a good substrate or a bad substrate and a host of different explanations have been suggested, such as the energy content of the nutrient, the protein investment required for efficient catabolism of the substrate, or limitations in membrane capacity for transporters of the substrate, all of which are actively debated. Here, we show instead that nutrient quality can be a plastic property that can be dialed by evolution or by genetic perturbations. While we report a correlation between nutrient quality and protein cost of substrate utilization, this correlation is not causal. Instead, nutrient quality is encoded by the proteome fraction of a core catabolic sector within a much larger co-regulated catabolic sector. Different nutrients thus enable bacteria to grow, but they also serve as a major signal that allows microbes to infer information about their environment. We propose that nutrient quality encoded in a combination regulatory architecture and enzymatic properties, serves as both as a map of the safety and reliability of the environment and as a regulatory mechanism implementing proteome allocation decisions.