ABSTRACT: Rifampicin hampers transcription, disrupting bacterial gene regulatory networks (GRN). Using RNA-seq, We investigated whether the GRN of susceptible E. coli has mechanisms that influence gene responses to non-lethal concentrations of rifampicin. We found that, over time, the transcriptome first diverged but then partially realigned with the control. Also, many genes were repressed, others activated. Some responded early (transiently or persistently), while others were late or switched responses suggesting the influence of diverse early and late mechanisms. Meanwhile, RNAP levels increased early, partially explaining how some genes were activated. Other mechanisms influencing genes response timing and magnitude were the promoters’ nucleotide composition, the transcription factor network, neighboring genes, DNA supercoiling buildup, σ32, σ38, and σ70, (p)ppGpp, and the global regulators fis, fnr, and marA. Finally, we found that orthologous genes of the evolutionarily distant M. tuberculosis and E. coli have correlated responses, suggesting a similar transcriptional program to promote survivability. Further, in both species, closely spaced genes have similar responses suggesting similar underlying mechanisms.
