One of the major ways of acquiring multidrug resistance in bacteria is via drug influx and efflux pathways. Here, we show that E. coli with compromised Rho-dependent transcription termination function has enhanced broad-spectrum antibiotic susceptibility, which arises from the inefficient TolC-efflux process and increased permeability of the membrane. The Rho mutants have altered morphology, distinct cell surface, and increased levels of lipopolysaccharide in their outer membrane, which might have rendered the TolC efflux pumps inefficient. These alterations are due to the upregulations of poly-N-acetyl-glucosamine and lipopolysaccharide synthesis operons because of inefficient Rho functions. The Rho mutants are capable of growing on various dipeptides and carbohydrate sources, unlike their WT counterpart. Dipeptides uptake arises from the upregulations of the di-peptide permease operon in these mutants. The metabolomics of the Rho mutants revealed the presence of a high level of novel metabolites. Accumulation of these metabolites in these Rho mutants might titrate out the TolC-efflux pumps, which could further reduce their efficiency. We conclude that the transcription termination factor, Rho, regulates the broad-spectrum antibiotic susceptibility of E. coli through multipartite pathways in a TolC-dependent manner. The involvement of Rho-dependent termination in multiple pathways and its association with antibiotic susceptibility should make Rho-inhibitors useful in the anti-bacterial treatment regimen.

获得细菌多药耐药性的主要方法之一是通过药物流入和流出途径。在这里，我们表明大肠杆菌Rho依赖的转录终止功能受损的人具有增强的广谱抗生素敏感性，这是由于低效的TolC外排过程和膜通透性增加所致。Rho突变体改变了形态，改变了细胞表面，并在其外膜中增加了脂多糖的水平，这可能使TolC外排泵效率低下。这些改变是由于无效的Rho功能导致聚-N-乙酰基-葡萄糖胺和脂多糖合成操纵子的上调。Rho突变体能够在各种二肽和碳水化合物来源上生长，与它们的WT对应物不同。在这些突变体中，二肽渗透酶操纵子的上调引起二肽的摄取。Rho突变体的代谢组学揭示了高水平的新型代谢产物的存在。这些代谢产物在这些Rho突变体中的积累可能会滴定TolC外排泵，这可能会进一步降低其效率。我们得出的结论是，转录终止因子Rho可以调节广谱抗生素的敏感性大肠杆菌通过多径途径以TolC依赖的方式进行。Rho依赖终止参与多种途径及其与抗生素敏感性的关联应使Rho抑制剂可用于抗菌治疗方案。