Regulatory perturbations of ribosome allocation in bacteria reshape 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 profile of two sets of fast-growing mutants of Escherichia coli K-12 MG1655. Mutants with 3 copies of the stronger ribosomal RNA operons grew faster than the wild-type strain in minimal media and show similar phenotype to previously studied rpoB mutants. All of them displayed increased ribosomal content, a longer diauxic shift and a reduced activity of the aceBAK operon, indicative of repressed gluconeogenic pathways. Transcriptomic profiles of fast-growing mutants showed common downregulation of hedging functions and upregulated growth functions. Proteome allocation estimations showed an increase in the growth-related proteome for fast-growing strains, but not an increased cellular budget for recombinant protein production. These results show that two different regulatory perturbations (rRNA promoters or rpoB mutations) increasing ribosomal allocation optimize the proteome for growth with a concomitant fitness cost. Overall design: mRNA of exponentially growing E. coli mutants in M9 minimal medium supplemented with glucose