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Targeting Bacterial Antioxidant Systems for Antibiotics Development

[ Vol. 27 , Issue. 12 ]

Author(s):

Xiaoyuan Ren*, Lili Zou and Arne Holmgren*   Pages 1922 - 1939 ( 18 )

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.

Keywords:

Multi-drug resistant bacteria, antibiotics, ROS, thioredoxin system, glutathione system, ebselen, silver.

Affiliation:

Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm



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