Engineering monolayer poration for rapid exfoliation of microbial membranes

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

PYNE Alice;  PFEIL Marc-Philipp;  BENNETT Isabel;  RAVI Jascindra;  IAVICOLI Patrizia;  LAMARRE Baptiste;  ROETHKE Anita;  RAY Santanu;  JIANG Haibo;  BELLA Angelo;  REISINGER Berndt;  YIN Daniel;  LITTLE Benjamin;  MUNOZ-GARCIA Juan C.;  CERASOLI Eleonora;  JUDGE Peter;  FARUQUI Nilofar;  CALZOLAI Luigi;  HENRION André;  MARTYNA Glenn;  GROVENOR Chris;  CRAIN Jason;  HOOGENBOOM Bart W.;  WATTS Anthony;  RYADNOV Maxim G.; 

2017-07-07

ROYAL SOC CHEMISTRY

JRC105545

2041-6520,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC105545,   

10.1039/c6sc02925f,