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Engineering Chirally Blind Protein Pseudocapsids into Antibacterial Persisters.

Published version
Peer-reviewed

Type

Article

Change log

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.

Description

Keywords

antimicrobial resistance, artificial pseudocapsids, nanopores, persister cells, protein design, superbugs, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Cell Survival, Escherichia coli, Microbial Sensitivity Tests, Models, Molecular, Particle Size, Protein Engineering, Protein Folding, Surface Properties

Journal Title

ACS Nano

Conference Name

Journal ISSN

1936-0851
1936-086X

Volume Title

Publisher

American Chemical Society (ACS)
Sponsorship
Medical Research Council (MR/N002660/1)
Medical Research Council (MR/P007201/1)
Economic and Social Research Council (ES/S000186/1)
Medical Research Council (G1001787)