Depletion of multidrug‐resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion. Issue 22 (25th September 2020)

• Record Type: Journal Article
• Authors: Wang, Peng; Wang, Jun; Xie, Zonglan; Zhou, Jingxuan; Lu, Qianqian; Zhao, Ying; Dong, Chuanjiang; Zou, Lili
• Is Part Of: Journal of cellular and molecular medicine. Volume 24:Issue 22(2020)
• Page Start: 13139
• Page End: 13150
• Publication Date: 2020-09-25
• Subjects: ebselen -- glutathione -- redox homeostasis -- silver ion -- thioredoxin reductase -- uropathogenic Escherichia coli; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.15920
• Languages: English
• ISSNs: 1582-1838

Abstract

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‐α (TNF‐α) and interferon‐γ (IFN‐γ) 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.