Regulatory Perturbations of Ribosome Allocation Optimize the Growth Proteome with a Trade-Off in Adaptation Capacity

Bacteria regulate their cellular resource allocation to enable their fast growth-adaptation to a variety of environmental niches. We studied the ribosomal allocation, growth and expression profiles of two sets of fast-growing mutants of Escherichia coli K-12 MG1655. Mutants with only 3 copies of the strongest ribosomal RNA operons grew faster than the wild-type strain in minimal media and show similar phenotype to previously studied rpoB mutants. Both fastgrowing strains showed higher ribosomal content rather than higher ribosomal efficiency. Expression profiles of fast-growing mutants shared downregulation of hedging functions and upregulated growth functions. Mutants showed longer diauxic shifts and reduced activity of gluconeogenic promoters during glucose-acetate shifts, suggesting reduced availability of the RNA Polymerase for expressing hedging proteome. These results show that the regulation of ribosomal allocation underlies the growth/hedging phenotypes obtained from laboratory evolution experiments. We show how two different regulatory perturbations (rRNA promoters or rpoB mutations) optimize the proteome for growth with a concomitant fitness cost.