Growth rate variations in Escherichia coli strains arise from differential expression of non-utilized proteins

Growth is fundamental to microbial life, shaping cells, their surroundings, and ecological roles. Seminal studies over decades have elucidated that coordinated metabolic and biosynthetic processes promote efficient and fast growth, with protein synthesis at the core. However, the variation in growth rates observed across environments remains physiologically puzzling. For instance, the model organism E. coli, grows much faster on glucose than on other carbon sources requiring similar metabolic pathways. To gain a mechanistic understanding of the origin of this growth variation, we systematically quantified the growth behavior of different E. coli strains, going beyond commonly studied lab strains. Despite highly similar sequences of their core metabolic and biosynthetic genes, we observed striking growth rate variations across strains for growth in the same condition. Using complementary biochemical, proteomics and genetic perturbation approach, we demonstrated that while the overall ability of strains to promote protein synthesis and biomass accumulation is similar, it is the differential expression of apparently non-needed proteins regulated by cAMP that drive growth rate variation by depletion resources away from the synthesis of those proteins required for growth.