Sub-inhibitory concentrations (sub-MIC) of antimicrobial agents can lead to genetic changes in bacteria, modulating the expression of genes related to bacterial stress and leading to drug resistance. Herein we describe the impact of sub-MIC of ciprofloxacin and nitrofurantoin on three uropathogenic Escherichia coli strains. Disk-diffusion assays with different antimicrobial agents were tested to detect phenotype alterations, and quantitative real-time PCR (qRT-PCR) was performed to analyze the expression of ompF and recA genes. Significant reduction on the susceptibility to ciprofloxacin and nitrofurantoin was detected on disk diffusion test. The qRT-PCR results revealed a 1.2-4.7 increase in recA expression in all E. coli studied, while the ompF expression varied. Because RecA was pointed as an important component to the development of drug resistance, molecular docking studies were performed with three experimentally known inhibitors of this enzyme. These studies aimed to understand the inhibitory binding mode of such compounds. The results confirmed the ADP/ATP binding site as a potential site of inhibitor recognition and a binding mode based on π-stacking interactions with Tyr103 and hydrogen bonds with Tyr264. These findings can be useful for guiding the search and design of new antimicrobial agents, mainly concerning the treatment of infections with resistant bacterial strains.

中文翻译：

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暴露于亚抑制性环丙沙星和硝基呋喃妥因浓度会增加尿路致病性大肠杆菌中recA基因的表达：RecA蛋白作为药物靶标的作用。

抗菌剂的亚抑制浓度（sub-MIC）可以导致细菌发生遗传变化，从而调节与细菌应激相关的基因表达并导致耐药性。在本文中，我们描述了环丙沙星和呋喃妥因的亚MIC对三种尿路致病性大肠杆菌菌株的影响。测试了使用不同抗菌剂进行的磁盘扩散测定法以检测表型改变，并进行了实时定量PCR（qRT-PCR）分析ompF和recA基因的表达。在纸片扩散试验中发现对环丙沙星和呋喃妥因的敏感性显着降低。qRT-PCR结果表明，在所有研究的大肠杆菌中recA表达增加了1.2-4.7，而ompF表达却有所不同。由于RecA被认为是耐药性发展的重要组成部分，因此使用三种实验上已知的该酶抑制剂进行了分子对接研究。这些研究旨在了解此类化合物的抑制性结合模式。结果证实了ADP / ATP结合位点是抑制剂识别的潜在位点，并且是基于与Tyr103的π-堆叠相互作用和与Tyr264的氢键的结合方式。这些发现可用于指导寻找和设计新的抗微生物剂，主要涉及抗药性细菌感染的治疗。结果证实了ADP / ATP结合位点是抑制剂识别的潜在位点，并且是基于与Tyr103的π-堆叠相互作用和与Tyr264的氢键的结合方式。这些发现可用于指导寻找和设计新的抗微生物剂，主要涉及抗药性细菌感染的治疗。结果证实了ADP / ATP结合位点是抑制剂识别的潜在位点，并且是基于与Tyr103的π堆积相互作用和与Tyr264的氢键的结合模式。这些发现可用于指导寻找和设计新的抗微生物剂，主要涉及抗药性细菌感染的治疗。