A microfluidic platform for the characterisation of membrane active antimicrobials.
Royal Society of Chemistry (RSC)
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Al Nahas, K., Cama, J., Schaich, M., Hammond, K., Deshpande, S., Dekker, C., Ryadnov, M., & et al. (2019). A microfluidic platform for the characterisation of membrane active antimicrobials.. Lab Chip, 19 (5), 837-844. https://doi.org/10.1039/c8lc00932e
The spread of bacterial resistance against conventional antibiotics generates a great need for the discovery of novel antimicrobials. Polypeptide antibiotics constitute a promising class of antimicrobial agents that favour attack on bacterial membranes. However, efficient measurement platforms for evaluating their mechanisms of action in a systematic manner are lacking. Here we report an integrated lab-on-a-chip multilayer microfluidic platform to quantify the membranolytic efficacy of such antibiotics. The platform is a biomimetic vesicle-based screening assay, which generates giant unilamellar vesicles (GUVs) in physiologically relevant buffers on demand. Hundreds of these GUVs are individually immobilised downstream in physical traps connected to separate perfusion inlets that facilitate controlled antibiotic delivery. Antibiotic efficacy is expressed as a function of the time needed for an encapsulated dye to leak out of the GUVs as a result of antibiotic treatment. This proof-of-principle study probes the dose response of an archetypal polypeptide antibiotic cecropin B on GUVs mimicking bacterial membranes. The results of the study provide a foundation for engineering quantitative, high-throughput microfluidics devices for screening antibiotics.
Cell Membrane, Insect Proteins, Anti-Bacterial Agents, Microfluidic Analytical Techniques, Drug Evaluation, Preclinical, Unilamellar Liposomes
-Trinity College, University of Cambridge (Trinity-Henry Barlow Scholarship) -H2020 European Research Council Advanced grants SynDiv (no. 669598), Consolidator Grant Designer- Pores (no. 647144) -Nederlandse Organisatie voor Wetenschappelijk Onderzoek Frontiers of Nanoscience program -Winton Programme for the Physics of Sustainability -Biotechnology and Biological Sciences Research Council -Friedrich-Naumann-Foundation -National Physical Laboratory EPSRC CASE -Department for Business, Energy & Industrial Strategy -European Metrology Research Programme (EMRP)
Biotechnology and Biological Sciences Research Council (BB/M008827/1)
European Research Council (647144)
National Physical Laboratory (NPL) (Unknown)
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External DOI: https://doi.org/10.1039/c8lc00932e
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288336
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/