A decrease in transcription capacity limits growth rate upon translation inhibition

In bacterial cells, inhibition of ribosomes by sublethal concentrations of antibiotics leads to a decrease in growth rate despite an increase in ribosome content. This has been proposed to result from a decrease in the resources available for the production of non-ribosomal proteins that become limiting for cellular metabolism, mediated by changes in ppGpp concentration. Here, by the comparison of the activity of promoters that are differentially regulated by ppGpp and with different affinities for RNAP, we show that increased ribosome inhibition instead results in a decrease in total RNAP activity, independently of the changes in ppGpp. This is due to the decrease in ribosome processivity which affects more strongly the translation of longer genes, such as those coding for the β and β’ subunits of RNAP, amongst the longest genes in the E. coli genome, while the expression of the very short ribosomal proteins is not limited to the same extent. Furthermore, the decrease in the total amount of free RNAP favors the expression of genes with promoters with a high RNAP affinity, such as ribosomal promoters, over the expression of other, growth-limiting, proteins. The decrease in transcription capacity could thus lead to increased survival whenever ribosome activity is compromised.