{"title":"黄金药物作为粘菌素佐剂对抗MCR-1产生细菌","authors":"Qi Zhang, Minji Wang, Xuqiao Hu, Aixin Yan, Pak-Leung Ho, Hongyan Li, Hongzhe Sun","doi":"10.1007/s00775-022-01983-y","DOIUrl":null,"url":null,"abstract":"<div><p>The emergence and rapid spread of the mobile colistin resistance gene <i>mcr-1</i> 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 <i>mcr-1</i>-positive bacteria. Herein, we uncovered more gold-based drugs and nanoparticles, and found that they exhibited varying degree of synergisms with colistin on killing <i>mcr-1</i>-positive bacteria. However, pre-activation of the drugs by either glutathione or <i>N</i>-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 <i>mcr-1</i>-positive bacterial infections, but also undoubtedly opens a new horizon for metabolism details of gold-based drugs in overcoming antimicrobial resistance.</p><h3>Graphical abstract</h3>\n <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\n </div>","PeriodicalId":603,"journal":{"name":"JBIC Journal of Biological Inorganic Chemistry","volume":"28 2","pages":"225 - 234"},"PeriodicalIF":2.7000,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Gold drugs as colistin adjuvants in the fight against MCR-1 producing bacteria\",\"authors\":\"Qi Zhang, Minji Wang, Xuqiao Hu, Aixin Yan, Pak-Leung Ho, Hongyan Li, Hongzhe Sun\",\"doi\":\"10.1007/s00775-022-01983-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The emergence and rapid spread of the mobile colistin resistance gene <i>mcr-1</i> 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 <i>mcr-1</i>-positive bacteria. Herein, we uncovered more gold-based drugs and nanoparticles, and found that they exhibited varying degree of synergisms with colistin on killing <i>mcr-1</i>-positive bacteria. However, pre-activation of the drugs by either glutathione or <i>N</i>-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 <i>mcr-1</i>-positive bacterial infections, but also undoubtedly opens a new horizon for metabolism details of gold-based drugs in overcoming antimicrobial resistance.</p><h3>Graphical abstract</h3>\\n <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\\n </div>\",\"PeriodicalId\":603,\"journal\":{\"name\":\"JBIC Journal of Biological Inorganic Chemistry\",\"volume\":\"28 2\",\"pages\":\"225 - 234\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-01-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JBIC Journal of Biological Inorganic Chemistry\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00775-022-01983-y\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JBIC Journal of Biological Inorganic Chemistry","FirstCategoryId":"1","ListUrlMain":"https://link.springer.com/article/10.1007/s00775-022-01983-y","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Gold drugs as colistin adjuvants in the fight against MCR-1 producing bacteria
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.
期刊介绍：
Biological inorganic chemistry is a growing field of science that embraces the principles of biology and inorganic chemistry and impacts other fields ranging from medicine to the environment. JBIC (Journal of Biological Inorganic Chemistry) seeks to promote this field internationally. The Journal is primarily concerned with advances in understanding the role of metal ions within a biological matrix—be it a protein, DNA/RNA, or a cell, as well as appropriate model studies. Manuscripts describing high-quality original research on the above topics in English are invited for submission to this Journal. The Journal publishes original articles, minireviews, and commentaries on debated issues.
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