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  • Title: Reactive oxygen species and uspA overexpession: an alternative bacterial response toward selection and maintenance of multidrug resistance in clinical isolates of uropathogenic E. coli.
    Author: Bandyopadhyay D, Mukherjee M.
    Journal: Eur J Clin Microbiol Infect Dis; 2020 Sep; 39(9):1753-1760. PubMed ID: 32399681.
    Abstract:
    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.
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