Issue 2, 2017

Engineering monolayer poration for rapid exfoliation of microbial membranes

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.

Graphical abstract: Engineering monolayer poration for rapid exfoliation of microbial membranes

Supplementary files

Article information

Article type
Edge Article
Submitted
03 Jul 2016
Accepted
25 Sep 2016
First published
26 Sep 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2017,8, 1105-1115

Author version available

Engineering monolayer poration for rapid exfoliation of microbial membranes

A. Pyne, M. Pfeil, I. Bennett, J. Ravi, P. Iavicoli, B. Lamarre, A. Roethke, S. Ray, H. Jiang, A. Bella, B. Reisinger, D. Yin, B. Little, J. C. Muñoz-García, E. Cerasoli, P. J. Judge, N. Faruqui, L. Calzolai, A. Henrion, G. J. Martyna, C. R. M. Grovenor, J. Crain, B. W. Hoogenboom, A. Watts and M. G. Ryadnov, Chem. Sci., 2017, 8, 1105 DOI: 10.1039/C6SC02925F

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