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Engineering monolayer poration for rapid exfoliation of microbial membranes

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journal contribution
posted on 12.12.2016, 18:39 by A. Pyne, M-P. 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, Maxim G. Ryadnov
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.

Funding

We thank the Bechinger group for their advice and support for the work, Hasan Alkassem for his help with AFM imaging and the EPSRC IRC in Early-Warning Sensing Systems for Infectious Diseases (EP/K031953/1) for use of research facilities. We acknowledge funding from the United Kingdom's Department of Business, Innovation and Skills, Engineering and Physical Sciences Research Council (EP/G036675/1 and EP/ M506448/1), Biotechnology and Biological Sciences Research Council (BB/J006254/1) and the European Metrology Research Programme (EMRP) projects. The EMRP is jointly funded by the EMRP participating countries within EURAMET and the European Union.

History

Citation

Chemical Science, 2017

Author affiliation

/Organisation/COLLEGE OF SCIENCE AND ENGINEERING/Department of Chemistry

Version

VoR (Version of Record)

Published in

Chemical Science

Publisher

Royal Society of Chemistry

issn

2041-6520

eissn

2041-6539

Acceptance date

25/09/2016

Available date

12/12/2016

Publisher version

http://pubs.rsc.org/en/Content/ArticleLanding/2017/SC/C6SC02925F#!divAbstract

Notes

Electronic supplementary information (ESI) available: Materials and methods, microscopy, spectroscopy, molecular dynamics and spectrometry data. See DOI: 10.1039/c6sc02925f

Language

en

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