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A microfluidic platform for the characterisation of membrane active antimicrobials

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Abstract

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.

Graphical abstract: A microfluidic platform for the characterisation of membrane active antimicrobials

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Publication details

The article was received on 03 Sep 2018, accepted on 05 Dec 2018 and first published on 30 Jan 2019


Article type: Paper
DOI: 10.1039/C8LC00932E
Citation: Lab Chip, 2019, Advance Article
  • Open access: Creative Commons BY license
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    A microfluidic platform for the characterisation of membrane active antimicrobials

    K. Al Nahas, J. Cama, M. Schaich, K. Hammond, S. Deshpande, C. Dekker, M. G. Ryadnov and U. F. Keyser, Lab Chip, 2019, Advance Article , DOI: 10.1039/C8LC00932E

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