Engineering chirally blind protein pseudocapsids into antibacterial persisters
dc.contributor.author | Kepiro, IE | |
dc.contributor.author | Marzuoli, I | |
dc.contributor.author | Hammond, K | |
dc.contributor.author | Ba, X | |
dc.contributor.author | Lewis, H | |
dc.contributor.author | Shaw, M | |
dc.contributor.author | Gunnoo, SB | |
dc.contributor.author | De Santis, E | |
dc.contributor.author | Łapińska, U | |
dc.contributor.author | Pagliara, S | |
dc.contributor.author | Holmes, MA | |
dc.contributor.author | Lorenz, CD | |
dc.contributor.author | Hoogenboom, BW | |
dc.contributor.author | Fraternali, F | |
dc.contributor.author | Ryadnov, MG | |
dc.date.accessioned | 2020-02-28T11:55:38Z | |
dc.date.issued | 2020-01-25 | |
dc.description.abstract | Antimicrobial 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.sponsorship | Medical Research Council | en_GB |
dc.identifier.citation | Vol. 14, No. 2, pp. 1609-1622 | en_GB |
dc.identifier.doi | 10.1021/acsnano.9b06814 | |
dc.identifier.grantnumber | MCPC17189 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/41044 | |
dc.language.iso | en | en_GB |
dc.publisher | American Chemical Society | en_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.subject | protein design | en_GB |
dc.subject | antimicrobial resistance | en_GB |
dc.subject | artificial pseudocapsids | en_GB |
dc.subject | persister cells | en_GB |
dc.subject | superbugs | en_GB |
dc.subject | nanopores | en_GB |
dc.title | Engineering chirally blind protein pseudocapsids into antibacterial persisters | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-02-28T11:55:38Z | |
dc.identifier.issn | 1936-0851 | |
dc.description | This is the final version. Available from the American Chemical Society via the DOI in this record. | en_GB |
dc.identifier.eissn | 1936-086X | |
dc.identifier.journal | ACS Nano | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-12-03 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-12-03 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-02-28T11:48:30Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-02-28T11:55:47Z | |
refterms.panel | A | en_GB |
Files in this item
This item appears in the following Collection(s)
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.