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dc.contributor.authorKepiro, IE
dc.contributor.authorMarzuoli, I
dc.contributor.authorHammond, K
dc.contributor.authorBa, X
dc.contributor.authorLewis, H
dc.contributor.authorShaw, M
dc.contributor.authorGunnoo, SB
dc.contributor.authorDe Santis, E
dc.contributor.authorŁapińska, U
dc.contributor.authorPagliara, S
dc.contributor.authorHolmes, MA
dc.contributor.authorLorenz, CD
dc.contributor.authorHoogenboom, BW
dc.contributor.authorFraternali, F
dc.contributor.authorRyadnov, MG
dc.date.accessioned2020-02-28T11:55:38Z
dc.date.issued2020-01-25
dc.description.abstractAntimicrobial resistance stimulates the search for antimicrobial forms that may be less subject to acquired resistance. Here we report a conceptual design of protein pseudocapsids exhibiting a broad spectrum of antimicrobial activities. Unlike conventional antibiotics, these agents are effective against phenotypic bacterial variants, while clearing "superbugs" in vivo without toxicity. The design adopts an icosahedral architecture that is polymorphic in size, but not in shape, and that is available in both l and d epimeric forms. Using a combination of nanoscale and single-cell imaging we demonstrate that such pseudocapsids inflict rapid and irreparable damage to bacterial cells. In phospholipid membranes they rapidly convert into nanopores, which remain confined to the binding positions of individual pseudocapsids. This mechanism ensures precisely delivered influxes of high antimicrobial doses, rendering the design a versatile platform for engineering structurally diverse and functionally persistent antimicrobial agents.en_GB
dc.description.sponsorshipMedical Research Councilen_GB
dc.identifier.citationVol. 14, No. 2, pp. 1609-1622en_GB
dc.identifier.doi10.1021/acsnano.9b06814
dc.identifier.grantnumberMCPC17189en_GB
dc.identifier.urihttp://hdl.handle.net/10871/41044
dc.language.isoenen_GB
dc.publisherAmerican Chemical Societyen_GB
dc.rights© The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. en_GB
dc.subjectprotein designen_GB
dc.subjectantimicrobial resistanceen_GB
dc.subjectartificial pseudocapsidsen_GB
dc.subjectpersister cellsen_GB
dc.subjectsuperbugsen_GB
dc.subjectnanoporesen_GB
dc.titleEngineering chirally blind protein pseudocapsids into antibacterial persistersen_GB
dc.typeArticleen_GB
dc.date.available2020-02-28T11:55:38Z
dc.identifier.issn1936-0851
dc.descriptionThis is the final version. Available from the American Chemical Society via the DOI in this record. en_GB
dc.identifier.eissn1936-086X
dc.identifier.journalACS Nanoen_GB
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2019-12-03
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2019-12-03
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2020-02-28T11:48:30Z
refterms.versionFCDVoR
refterms.dateFOA2020-02-28T11:55:47Z
refterms.panelAen_GB


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© The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 
Except where otherwise noted, this item's licence is described as © The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.