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Depletion of multidrug-resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion.

ABSTRACT: Ebselen, an organo-selenium compound with well-characterized toxicology and pharmacology, recently exhibited potent antibacterial activity against glutathione (GSH)-negative bacteria by disrupting redox homeostasis. In this paper, we show that ebselen and silver ion in combination exert strong bactericidal activity against multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) BC1, a model MDR GSH-positive bacterium. The mechanisms were found to involve consumption of total intracellular GSH and inhibition of thioredoxin reductase activity, which was highly related to reactive oxygen species up-regulation. Furthermore, the therapeutic efficacy of ebselen and silver ion against UPEC-induced cystitis was assessed in a mouse model. Treatment with ebselen and silver ion significantly reduced bacterial loads, down-regulated the expression levels of tumour necrosis factor-? (TNF-?) and interferon-? (IFN-?) on-site and decreased white/red blood cell counts in mild cystitis model mice, which demonstrated the anti-inflammatory property of these agents. In addition, ebselen and silver ion also exhibited significantly high protective ability (100%) against acute cystitis infections. These results together may lay the foundation for further analysis and development of ebselen and silver ion as antibacterial agents for treatment of MDR UPEC infections.

SUBMITTER: Wang P

PROVIDER: S-EPMC7701569 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Depletion of multidrug-resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion.

Wang Peng P Wang Jun J Xie Zonglan Z Zhou Jingxuan J Lu Qianqian Q Zhao Ying Y Dong Chuanjiang C Zou Lili L

Journal of cellular and molecular medicine 20200925 22

Ebselen, an organo-selenium compound with well-characterized toxicology and pharmacology, recently exhibited potent antibacterial activity against glutathione (GSH)-negative bacteria by disrupting redox homeostasis. In this paper, we show that ebselen and silver ion in combination exert strong bactericidal activity against multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) BC1, a model MDR GSH-positive bacterium. The mechanisms were found to involve consumption of total intracellula ...[more]

PMID: 32975381

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Project description:Introduction:Extended-spectrum ?-lactamases (ESBL) among Gram-negative bacteria, predominantly Escherichia coli (E. coli), in Nepal, have been rising. The main objectives of this study were to determine the prevalence of uropathogenic E. coli, antibiotic resistance, ESBLs, ABLs (AmpC type ?-lactamases), MBLs (metallo-?-lactamases) and KPCs (Klebsiella pneumoniae carbapenemases) and their correlation with plasmid profiling patterns among patients with urinary tract infections in a tertiary hospital in Kathmandu, Nepal. Methods:The mid-stream urine samples collected from patients were inoculated in cystine-lactose-electrolyte-deficient (CLED) agar plates. E. coli producing ESBLs, ABLs, MBLs/KPC were identified phenotypically using standard microbiological methods. Plasmids were extracted by alkaline lysis method from E. coli isolates and profiled using agarose gel electrophoresis. Results:Out of the total 2661 urine samples, E. coli were isolated in 64.34% (507/788), among which 170 (33.53%) were multidrug-resistant (MDR) isolates. All MDR isolates were resistant to amoxicillin and third-generation cephalosporins but were highly sensitive to imipenem (94.12%, 160/170), amikacin (92.94%, 158/170) and nitrofurantoin (86.47%, 147/170). Among 170 MDR isolates, 78.2% (133/170) were ESBLs, 46.3% (50/170) were AmpC, 11.2% (19/170) were MBL and 0.6% (1/170) were KPC producers. Coproduction of ?-lactamases was detected in 24.12% (41/170) of isolates. E. coli isolates showed one plasmid (>33.5 kb), which was present in all the isolates. Overall, 44 different plasmid profile groups were identified based on molecular weight and number of plasmids. ?-Lactamase producers were relatively resistant to the higher number of antibiotics tested (?10) than non-producers (?8), and the number of plasmids were higher in ?-lactamase producers (?7) than those in non-producers (?5). Conclusion:The higher prevalence of the ESBLs, AmpCs, KPCs and MBLs along with their coproduction in E. coli isolates highlights the importance of routine surveillance of ESBLs, AmpCs, KPCs and MBLs in microbiology laboratories using various phenotypic methods.

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Depletion of multidrug-resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion.

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Depletion of multidrug-resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion.

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