1. Gold drugs as colistin adjuvants in the fight against MCR-1 producing bacteria.
- Author
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Zhang, Qi, Wang, Minji, Hu, Xuqiao, Yan, Aixin, Ho, Pak-Leung, Li, Hongyan, and Sun, Hongzhe
- Subjects
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COLISTIN , *ACETYLCYSTEINE , *X-ray crystallography , *GOLD , *SILVER nitrate , *DRUG resistance in microorganisms - Abstract
The emergence and rapid spread of the mobile colistin resistance gene mcr-1 among bacterial species and hosts significantly challenge the efficacy of "last-line" antibiotic colistin. Previously, we reported silver nitrate and auranofin serve as colistin adjuvants for combating mcr-1-positive bacteria. Herein, we uncovered more gold-based drugs and nanoparticles, and found that they exhibited varying degree of synergisms with colistin on killing mcr-1-positive bacteria. However, pre-activation of the drugs by either glutathione or N-acetyl cysteine, thus releasing and accumulating gold ions, is perquisite for their abilities to substitute zinc cofactor from MCR-1 enzyme. X-ray crystallography and biophysical studies further supported the proposed mechanism. This study not only provides basis for combining gold-based drugs and colistin for combating mcr-1-positive bacterial infections, but also undoubtedly opens a new horizon for metabolism details of gold-based drugs in overcoming antimicrobial resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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