Emergence of multidrug resistance (MDR) in uropathogenic E. coli (UPEC) demands alternative therapeutic interventions. Bactericidal antibiotics at their sub-inhibitory concentration stimulate production of reactive oxygen species (ROS) that results in oxidative stress, generates mutations, and alters transcription of different genes. Sub-inhibitory concentration of antibiotics facilitates selection of highly resistant population. Universal stress protein A (uspA) overexpression in MDR-UPEC at sub-inhibitory bactericidal antibiotics concentration was investigated to explore alternative survival strategy against them. Fifty clinical UPEC isolates were screened. Minimum inhibitory concentration (MIC) against three different bactericidal antibiotics (ciprofloxacin, CIP; ceftazidime, CAZ; gentamycin, GEN) was determined by broth dilution method; ROS production by DCFDA and overexpression of uspA by real-time PCR were determined at the sub-inhibitory concentration of antibiotics. DNA ladder formation and SEM studies were performed with drug untreated and treated samples. Statistical analysis was done by Student’s t test and Pearson’s correlation analysis; 25 out of 50 UPEC exhibited high MIC against CIP (> 200 μg/ml), CAZ (> 500 μg/ml), GEN (> 500 μg/ml), with varied ROS production (p ≤ 0.001) in treated than untreated controls. DNA ladder formation confirmed ROS production in drug-treated samples. SEM analysis revealed unaltered cell morphology in both untreated and drug-treated bacteria. uspA was universally overexpressed in all 25 UPEC. A significant correlation (p ≤ 0.001) between ROS production and uspA overexpression was observed in 19 out of 25 MDR isolates at sub-inhibitory doses of the bactericidal antibiotics. Therefore, this study highlights an alternative strategy that the MDR isolates may acquire when exposed to sub-inhibitory drug concentration for their survival.

尿路致病性大肠杆菌（UPEC）中多药耐药性（MDR）的出现需要其他治疗干预措施。处于亚抑制浓度的杀菌抗生素会刺激活性氧（ROS）的产生，从而导致氧化应激，产生突变并改变不同基因的转录。抗生素的亚抑制浓度有助于选择高抗药性人群。研究了在亚抑制性杀菌抗生素浓度下MDR-UPEC中普遍应激蛋白A（uspA）的过度表达，以探索针对它们的替代生存策略。筛选了50株临床UPEC分离株。通过肉汤稀释法测定对三种不同杀菌抗生素（环丙沙星，CIP；头孢他啶，CAZ；庆大霉素，GEN）的最小抑菌浓度（MIC）。在抗生素的亚抑制浓度下，确定了DCFDA产生的ROS和实时PCR过度表达uspA。用未经处理的和经过处理的样品进行DNA梯形形成和SEM研究。通过Student's t检验和Pearson相关分析进行统计分析。50个UPEC中有25个对CIP（> 200μg/ ml），CAZ（> 500μg/ ml），GEN（> 500μg/ ml）表现出高MIC，具有不同的ROS产生（p 与未处理的对照组相比，≤0.001）。DNA梯形的形成证实了药物处理样品中ROS的产生。SEM分析显示未经处理和经过药物处理的细菌的细胞形态均未改变。uspA在所有25个UPEC中普遍过表达。甲显著相关性（p  ROS生产和之间≤0.001）USPA在亚抑制的剂量的杀菌性抗生素在19中观察到的25株MDR过表达。因此，本研究强调了耐多药分离株在暴露于亚抑制药物浓度下生存时可能获得的替代策略。