Engineering monolayer poration for rapid exfoliation of microbial membranes

Alice Pyne, Marc Philipp Pfeil, Isabel Bennett, Jascindra Ravi, Patrizia Iavicoli, Baptiste Lamarre, Anita Roethke, Santanu Ray, Haibo Jiang, Angelo Bella, Bernd Reisinger, Daniel Yin, Benjamin Little, Juan C. Muñoz-García, Eleonora Cerasoli, Peter J. Judge, Nilofar Faruqui, Luigi Calzolai, Andre Henrion, Glenn J. MartynaChris R M Grovenor, Jason Crain, Bart W. Hoogenboom, Anthony Watts, Maxim G. Ryadnov

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1105-1115
Number of pages11
JournalChemical Science
Volume8
Issue number2
DOIs
Publication statusPublished - 2017

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    Pyne, A., Pfeil, M. P., Bennett, I., Ravi, J., Iavicoli, P., Lamarre, B., Roethke, A., Ray, S., Jiang, H., Bella, A., Reisinger, B., Yin, D., Little, B., Muñoz-García, J. C., Cerasoli, E., Judge, P. J., Faruqui, N., Calzolai, L., Henrion, A., ... Ryadnov, M. G. (2017). Engineering monolayer poration for rapid exfoliation of microbial membranes. Chemical Science, 8(2), 1105-1115. https://doi.org/10.1039/C6SC02925F