Antibiotic tolerance is associated with a broad and complex transcriptional response in E. coli

Antibiotic treatment kills a large portion of a population, while a small, tolerant subpopulation survives. Tolerant bacteria disrupt antibiotic efficacy and increase the likelihood that a population gains antibiotic resistance, a growing health concern. We examined how E. coli transcriptional networks changed in response to lethal ampicillin concentrations. We are the first to apply transcriptional regulatory network (TRN) analysis to antibiotic tolerance by leveraging existing knowledge and our transcriptional data. TRN analysis shows that gene expression changes specific to ampicillin treatment are likely caused by specific sigma and transcription factors typically regulated by proteolysis. These results demonstrate that to survive lethal concentration of ampicillin specific regulatory proteins change activity and cause a coordinated transcriptional response that leverages multiple gene systems.

Automated summary

Antibiotic treatment leads to the survival of a tolerant subpopulation within a bacterial population, increasing the risk of antibiotic resistance development. Research shows that specific regulatory proteins play a key role in enabling tolerance to lethal antibiotic concentrations by inducing coordinated transcriptional responses.