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

Autor: Lili Zou, Jingxuan Zhou, Jun Wang, Qianqian Lu, Peng Wang, Ying Zhao, Zonglan Xie, Chuanjiang Dong
Rok vydání: 2020
Předmět:
0301 basic medicine
Azoles
Male
Silver
Thioredoxin-Disulfide Reductase
Thioredoxin reductase
Microbial Sensitivity Tests
Isoindoles
medicine.disease_cause
Microbiology
03 medical and health sciences
chemistry.chemical_compound
Interferon-gamma
Mice
0302 clinical medicine
Drug Resistance
Multiple
Bacterial
Organoselenium Compounds
Cystitis
medicine
Animals
Uropathogenic Escherichia coli
glutathione
Escherichia coli
chemistry.chemical_classification
Inflammation
Ions
Reactive oxygen species
Mice
Inbred BALB C
redox homeostasis
Ebselen
Tumor Necrosis Factor-alpha
silver ion
thioredoxin reductase
Cell Biology
Glutathione
Original Articles
Anti-Bacterial Agents
Multiple drug resistance
Disease Models
Animal
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Molecular Medicine
Original Article
ebselen
Antibacterial activity
Reactive Oxygen Species
Oxidation-Reduction
Intracellular
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
Popis: 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.
Databáze: OpenAIRE
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