Synergistic therapeutic efficacy of ebselen and silver ions against multidrug-resistant Acinetobacter baumannii-induced urinary tract infections†
Ebselen (EbSe), an organo-selenium compound with well-characterized toxicology and pharmacology, exhibited potent antibacterial activity against glutathione (GSH)-positive bacteria when combined with silver ions (Ag+). In this paper, the strong bactericidal activity of EbSe–Ag+ against multidrug-resistant (MDR) Acinetobacter baumannii has been confirmed, and its efficacy was mainly based on the inhibition of thioredoxin reductase (TrxR) activity and the depletion of the total GSH amount. Moreover, the therapeutic effect of EbSe–Ag+ on urinary tract infection was assessed in a mouse model induced with A. baumannii 0361# strain. The treatment with EbSe–Ag+ significantly reduced the bacterial load and expression levels of the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in bladder lesions; meanwhile, the pathological experiment showed that A. baumannii-induced changes in EbSe–Ag+ treated mice were much attenuated than that in the control group. Thus, all the results obtained here may lay the foundation for further analysis and development of EbSe–Ag+ as potential antibacterial agents for MDR A. baumannii-induced urinary tract infection treatment.