Title: Engineering monolayer poration for rapid exfoliation of microbial membranes
Authors: PYNE ALICEPFEIL MARC-PHILIPPBENNETT ISABELRAVI JASCINDRAIAVICOLI PATRIZIALAMARRE BAPTISTEROETHKE ANITARAY SANTANUJIANG HAIBOBELLA ANGELOREISINGER BERNDTYIN DANIELLITTLE BENJAMINMUNOZ-GARCIA JUAN C.CERASOLI ELEONORAJUDGE PETERFARUQUI NILOFARCALZOLAI LUIGIHENRION ANDRÉMARTYNA GLENNGROVENOR CHRISCRAIN JASONHOOGENBOOM BART W.WATTS ANTHONYRYADNOV MAXIM G.
Citation: CHEMICAL SCIENCE vol. 8 no. 2 p. 1105-1115
Publisher: ROYAL SOC CHEMISTRY
Publication Year: 2017
JRC N°: JRC105545
ISSN: 2041-6520
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC105545
DOI: 10.1039/c6sc02925f
Type: Articles in periodicals and books
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
JRC Directorate:Health, Consumers and Reference Materials

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