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Article: Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors

TitleBismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors
Authors
Issue Date2018
PublisherNature Publishing Group: Nature Communications. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2018, v. 9, p. 439 How to Cite?
AbstractDrug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.
Persistent Identifierhttp://hdl.handle.net/10722/259163
ISSN
2015 Impact Factor: 11.329
2015 SCImago Journal Rankings: 6.539

 

DC FieldValueLanguage
dc.contributor.authorWANG, R-
dc.contributor.authorLAI, TP-
dc.contributor.authorGao, P-
dc.contributor.authorZhang, HM-
dc.contributor.authorHo, PL-
dc.contributor.authorWoo, PCY-
dc.contributor.authorMa, GX-
dc.contributor.authorKao, RYT-
dc.contributor.authorLi, H-
dc.contributor.authorSun, H-
dc.date.accessioned2018-09-03T04:02:32Z-
dc.date.available2018-09-03T04:02:32Z-
dc.date.issued2018-
dc.identifier.citationNature Communications, 2018, v. 9, p. 439-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/259163-
dc.description.abstractDrug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.-
dc.languageeng-
dc.publisherNature Publishing Group: Nature Communications. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleBismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors-
dc.typeArticle-
dc.identifier.emailGao, P: gaopeng@hku.hk-
dc.identifier.emailHo, PL: plho@hku.hk-
dc.identifier.emailWoo, PCY: pcywoo@hkucc.hku.hk-
dc.identifier.emailKao, RYT: rytkao@hkucc.hku.hk-
dc.identifier.emailLi, H: hylichem@hku.hk-
dc.identifier.emailSun, H: hsun@hku.hk-
dc.identifier.authorityHo, PL=rp00406-
dc.identifier.authorityWoo, PCY=rp00430-
dc.identifier.authorityKao, RYT=rp00481-
dc.identifier.authoritySun, H=rp00777-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-018-02828-6-
dc.identifier.hkuros287777-
dc.identifier.volume9-
dc.identifier.spage439-
dc.identifier.epage439-
dc.publisher.placeUnited Kingdom-

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