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Sci Rep. 2018 Jul 24;8(1):11131. doi: 10.1038/s41598-018-29313-w.

Synergistic antibacterial activity of silver with antibiotics correlating with the upregulation of the ROS production.

Author information

1
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
2
Translational Neuroscience & Neural Regeneration and Repair Institute/Institute of Cell Therapy, The People's Hospital of China Three Gorges University, 443000, Yichang, China.
3
Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
4
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77, Stockholm, Sweden. junlu@swu.edu.cn.
5
School of Pharmaceutical Sciences, Southwest University, 400715, Chongqing, China. junlu@swu.edu.cn.
6
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77, Stockholm, Sweden. arne.holmgren@ki.se.

Abstract

Thiol-dependent enzymes, including the thioredoxin (Trx) and glutathione (GSH) systems, have recently been found as promising bactericidal targets in multidrug-resistant (MDR) bacteria. We previously discovered that silver acted synergistically with ebselen in the inhibition of the Trx system and also resulted in a fast depletion of GSH in Gram-negative bacteria. Silver has been found by others to improve the sensitivity of bacteria to certain conventional antibiotics. Here, we found that the synergistic antibacterial effects of silver with four conventional antibiotics was correlated with the blockage of bacterial Trx system by silver. The synergistic antibacterial effect came along with the production of reactive oxygen species. All these results suggested that silver primarily enhanced the bactericidal activities of conventional antibiotics towards Gram-negative strains through the upregulation of ROS production.

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