Title:Targeting Bacterial Antioxidant Systems for Antibiotics Development
Volume: 27
Issue: 12
Author(s): Xiaoyuan Ren*, Lili Zou and Arne Holmgren*
Affiliation:
- Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm,Sweden
- Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm,Sweden
Keywords:
Multi-drug resistant bacteria, antibiotics, ROS, thioredoxin system, glutathione system, ebselen, silver.
Abstract: The emergence of multidrug-resistant bacteria has become an urgent issue in modern
medicine which requires novel strategies to develop antibiotics. Recent studies have supported
the hypothesis that antibiotic-induced bacterial cell death is mediated by Reactive
Oxygen Species (ROS). The hypothesis also highlighted the importance of antioxidant systems,
the defense mechanism which contributes to antibiotic resistance. Thioredoxin and glutathione
systems are the two major thiol-dependent systems which not only provide
antioxidant capacity but also participate in various biological events in bacteria, such as DNA
synthesis and protein folding. The biological importance makes them promising targets for
novel antibiotics development. Based on the idea, ebselen and auranofin, two bacterial thioredoxin
reductase inhibitors, have been found to inhibit the growth of bacteria lacking the GSH
efficiently. A recent study combining ebselen and silver exhibited a strong synergistic effect
against Multidrug-Resistant (MDR) Gram-negative bacteria which possess both thioredoxin
and glutathione systems. These drug-repurposing studies are promising for quick clinical usage
due to their well-known profile.