Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
Department of Biology and Microbiology, South Dakota State University, Brookings, SD, 57006, USA.
Sci Rep. 2021 Mar 17;11(1):6112. doi: 10.1038/s41598-021-85509-7.
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.
抗生素治疗会杀死大部分种群，而一小部分具有耐受性的亚群得以存活。具有耐受性的细菌会破坏抗生素的疗效，并增加种群获得抗生素耐药性的可能性，这是一个日益严重的健康问题。我们研究了大肠杆菌转录网络如何对致死浓度的氨苄青霉素做出反应。我们首次通过利用现有知识和我们的转录数据，将转录调控网络（TRN）分析应用于抗生素耐受性。TRN 分析表明，氨苄青霉素处理特有的基因表达变化可能是由特定的σ和转录因子引起的，这些因子通常受到蛋白酶的调控。这些结果表明，为了在致死浓度的氨苄青霉素中存活，特定的调节蛋白会改变活性，并引起协调的转录反应，利用多个基因系统。
