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.
Keyphrases
- multidrug resistant
- escherichia coli
- silver nanoparticles
- gold nanoparticles
- drug resistant
- klebsiella pneumoniae
- acinetobacter baumannii
- gram negative
- anti inflammatory
- reactive oxygen species
- red blood cell
- mouse model
- dendritic cells
- fluorescent probe
- transcription factor
- metabolic syndrome
- rheumatoid arthritis
- staphylococcus aureus
- skeletal muscle
- adipose tissue
- respiratory failure
- long non coding rna
- insulin resistance
- high glucose
- cystic fibrosis