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Engineering Chirally Blind Protein Pseudocapsids into Antibacterial Persisters

Kepiro, IE; Marzuoli, I; Hammond, K; Ba, X; Lewis, H; Shaw, M; Gunnoo, SB; ... Ryadnov, MG; + view all (2020) Engineering Chirally Blind Protein Pseudocapsids into Antibacterial Persisters. ACS Nano , 14 (2) pp. 1609-1622. 10.1021/acsnano.9b06814. Green open access

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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.

Type: Article
Title: Engineering Chirally Blind Protein Pseudocapsids into Antibacterial Persisters
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acsnano.9b06814
Publisher version: https://doi.org/10.1021/acsnano.9b06814
Language: English
Additional information: This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Keywords: antimicrobial resistance, artificial pseudocapsids, nanopores, persister cells, protein design, superbugs
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
URI: https://discovery.ucl.ac.uk/id/eprint/10089074
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