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Article: Re-sensitization of mcr carrying multidrug resistant bacteria to colistin by silver

TitleRe-sensitization of mcr carrying multidrug resistant bacteria to colistin by silver
Authors
Keywordsantimicrobial resistance
colistin
MCR-1
metalloenzymes
silver
Issue Date2022
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2022, v. 119, n. 11, article no. e2119417119 How to Cite?
AbstractColistin is considered the last-line antimicrobial for the treatment of multidrug-resistant gram-negative bacterial infections. The emergence and spread of superbugs carrying the mobile colistin resistance gene (mcr) have become the most serious and urgent threat to healthcare. Here, we discover that silver (Ag+), including silver nanoparticles, could restore colistin efficacy against mcr-positive bacteria. We show that Ag+inhibits the activity of the MCR-1 enzyme via substitution of Zn2+in the active site. Unexpectedly, a tetra-silver center was found in the active-site pocket of MCR-1 as revealed by the X-ray structure of the Ag-bound MCR-1, resulting in the prevention of substrate binding. Moreover, Ag+effectively slows down the development of higher-level resistance and reduces mutation frequency. Importantly, the combined use of Ag+at a low concentration with colistin could relieve dermonecrotic lesions and reduce the bacterial load of mice infected with mcr-1-carrying pathogens. This study depicts a mechanism of Ag+inhibition of MCR enzymes and demonstrates the potentials of Ag+as broad-spectrum inhibitors for the treatment of mcr-positive bacterial infection in combination with colistin.
Persistent Identifierhttp://hdl.handle.net/10722/313039
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Qi-
dc.contributor.authorWang, Runming-
dc.contributor.authorWang, Minji-
dc.contributor.authorLiu, Chunjiao-
dc.contributor.authorKoohi-Moghadam, Mohamad-
dc.contributor.authorWang, Haibo-
dc.contributor.authorHo, Pak Leung-
dc.contributor.authorLi, Hongyan-
dc.contributor.authorSun, Hongzhe-
dc.date.accessioned2022-05-26T07:00:09Z-
dc.date.available2022-05-26T07:00:09Z-
dc.date.issued2022-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2022, v. 119, n. 11, article no. e2119417119-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/313039-
dc.description.abstractColistin is considered the last-line antimicrobial for the treatment of multidrug-resistant gram-negative bacterial infections. The emergence and spread of superbugs carrying the mobile colistin resistance gene (mcr) have become the most serious and urgent threat to healthcare. Here, we discover that silver (Ag+), including silver nanoparticles, could restore colistin efficacy against mcr-positive bacteria. We show that Ag+inhibits the activity of the MCR-1 enzyme via substitution of Zn2+in the active site. Unexpectedly, a tetra-silver center was found in the active-site pocket of MCR-1 as revealed by the X-ray structure of the Ag-bound MCR-1, resulting in the prevention of substrate binding. Moreover, Ag+effectively slows down the development of higher-level resistance and reduces mutation frequency. Importantly, the combined use of Ag+at a low concentration with colistin could relieve dermonecrotic lesions and reduce the bacterial load of mice infected with mcr-1-carrying pathogens. This study depicts a mechanism of Ag+inhibition of MCR enzymes and demonstrates the potentials of Ag+as broad-spectrum inhibitors for the treatment of mcr-positive bacterial infection in combination with colistin.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectantimicrobial resistance-
dc.subjectcolistin-
dc.subjectMCR-1-
dc.subjectmetalloenzymes-
dc.subjectsilver-
dc.titleRe-sensitization of mcr carrying multidrug resistant bacteria to colistin by silver-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1073/pnas.2119417119-
dc.identifier.pmid35263219-
dc.identifier.pmcidPMC8931383-
dc.identifier.scopuseid_2-s2.0-85126173510-
dc.identifier.volume119-
dc.identifier.issue11-
dc.identifier.spagearticle no. e2119417119-
dc.identifier.epagearticle no. e2119417119-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000771756300005-

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