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Engineering monolayer poration for rapid exfoliation of microbial membranes

Pyne, A; Pfeil, MP; Bennett, I; Ravi, J; Iavicoli, P; Lamarre, B; Roethke, A; ... Ryadnov, MG; + view all (2017) Engineering monolayer poration for rapid exfoliation of microbial membranes. Chemical Science , 8 (2) pp. 1105-1115. 10.1039/C6SC02925F. Green open access

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Abstract

The spread of bacterial resistance to traditional antibiotics continues to stimulate the search for alternative antimicrobial strategies. All forms of life, from bacteria to humans, are postulated to rely on a fundamental host defense mechanism, which exploits the formation of open pores in microbial phospholipid bilayers. Here we predict that transmembrane poration is not necessary for antimicrobial activity and reveal a distinct poration mechanism that targets the outer leaflet of phospholipid bilayers. Using a combination of molecular-scale and real-time imaging, spectroscopy and spectrometry approaches, we introduce a structural motif with a universal insertion mode in reconstituted membranes and live bacteria. We demonstrate that this motif rapidly assembles into monolayer pits that coalesce during progressive membrane exfoliation, leading to bacterial cell death within minutes. The findings offer a new physical basis for designing effective antibiotics.

Type: Article
Title: Engineering monolayer poration for rapid exfoliation of microbial membranes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/C6SC02925F
Publisher version: http://dx.doi.org/10.1039/C6SC02925F
Language: English
Additional information: Open Access Article: This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence (http://creativecommons.org/licenses/by-nc/3.0/)
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
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
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology
URI: http://discovery.ucl.ac.uk/id/eprint/1542498
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