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Engineering effective antimicrobial agents

Engineering effective antimicrobial agents
Sep 11 2017

The JRC – in collaboration with other Research Institutions – identified and measured a new mechanism of antimicrobial activity.

They predicted, engineered and demonstrated antimicrobial monolayer poration. The visualisation in live bacteria demonstrated that bacterial cell death can happen within minutes. 

Membrane poration is fundamental to cell function. In particular, the spread of antimicrobial resistance re-emphasises poration as a means of fighting infections.

Starting from the hypothesis that transmembrane poration is not necessary for antimicrobial activity this study revealed a distinct mechanism that targets the outer leaflet of the phospholipid bilayers leading to monolayer poration rather than to the standard bilayer poration mechanism.

Based on the architecture of natural antimicrobial peptides, a research team from the JRC, NPL (UK), PTB (DE), Universities of Oxford (UK), of Edinburgh (UK), and of Western Austria and the IBM Thomas J Watson Research Center (USA), engineered a specific peptide motif.

This motif, instead of making holes in bacterial cells, would destroy the cell membranes by first incorporating into them and subsequent disintegration.

The new mode of action has been proved by a combination of molecular-scale and real-time imaging, spectroscopy and spectrometry approaches. The research demonstrates that the peptide structural motif developed during the project rapidly assembles into monolayer pits that coalesce during progressive membrane exfoliation, leading to bacterial cell death within minutes. 

These findings offer a new physical basis for designing effective antibiotics.

Read more in: A Pyne et al. "Engineering monolayer poration for rapid exfoliation of microbial membranes", Chemical Science 8 (2017) 1105-1115, doi: 10.1039/c6sc02925f