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- Publisher Website: 10.1038/s41467-020-18939-y
- Scopus: eid_2-s2.0-85092651109
- PMID: 33067430
- WOS: WOS:000582056600026
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Article: Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin
Title | Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin |
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Authors | |
Issue Date | 2020 |
Publisher | Nature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html |
Citation | Nature Communications, 2020, v. 11, p. article no. 5263 How to Cite? |
Abstract | Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, blaMBL and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-beta-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of beta-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-beta-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs. |
Persistent Identifier | http://hdl.handle.net/10722/293492 |
ISSN | 2023 Impact Factor: 14.7 2023 SCImago Journal Rankings: 4.887 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Sun, H | - |
dc.contributor.author | ZHANG, Q | - |
dc.contributor.author | Wang, R | - |
dc.contributor.author | Wang, H | - |
dc.contributor.author | WONG, YT | - |
dc.contributor.author | Wang, M | - |
dc.contributor.author | Hao, Q | - |
dc.contributor.author | Yan, A | - |
dc.contributor.author | Kao, RYT | - |
dc.contributor.author | Ho, PL | - |
dc.contributor.author | Li, H | - |
dc.date.accessioned | 2020-11-23T08:17:34Z | - |
dc.date.available | 2020-11-23T08:17:34Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Nature Communications, 2020, v. 11, p. article no. 5263 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/10722/293492 | - |
dc.description.abstract | Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, blaMBL and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-beta-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of beta-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-beta-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs. | - |
dc.language | eng | - |
dc.publisher | Nature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html | - |
dc.relation.ispartof | Nature Communications | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin | - |
dc.type | Article | - |
dc.identifier.email | Sun, H: hsun@hku.hk | - |
dc.identifier.email | Wang, R: u3002771@connect.hku.hk | - |
dc.identifier.email | Wang, H: wanghaib@hku.hk | - |
dc.identifier.email | Hao, Q: qhao@hku.hk | - |
dc.identifier.email | Yan, A: ayan8@hku.hk | - |
dc.identifier.email | Kao, RYT: rytkao@hkucc.hku.hk | - |
dc.identifier.email | Ho, PL: plho@hku.hk | - |
dc.identifier.email | Li, H: hylichem@hku.hk | - |
dc.identifier.authority | Sun, H=rp00777 | - |
dc.identifier.authority | Hao, Q=rp01332 | - |
dc.identifier.authority | Yan, A=rp00823 | - |
dc.identifier.authority | Kao, RYT=rp00481 | - |
dc.identifier.authority | Ho, PL=rp00406 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41467-020-18939-y | - |
dc.identifier.pmid | 33067430 | - |
dc.identifier.pmcid | PMC7568570 | - |
dc.identifier.scopus | eid_2-s2.0-85092651109 | - |
dc.identifier.hkuros | 318904 | - |
dc.identifier.volume | 11 | - |
dc.identifier.spage | article no. 5263 | - |
dc.identifier.epage | article no. 5263 | - |
dc.identifier.isi | WOS:000582056600026 | - |
dc.publisher.place | United Kingdom | - |