Issue 5, 2019

A microfluidic platform for the characterisation of membrane active antimicrobials

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

Supplementary files

Article information

Article type
Paper
Submitted
03 sep 2018
Accepted
05 dec 2018
First published
30 jan 2019
This article is Open Access
Creative Commons BY license

Lab Chip, 2019,19, 837-844

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, 19, 837 DOI: 10.1039/C8LC00932E

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