Liposome-based microfluidic platform for standardized analysis of antibacterial compounds

Dr. C. Nehls1) – Research Center Borstel, Germany

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1.

Dr. Christian NehlsResearch Center Borstel, Leibniz Lung Center, Parkallee 1-40, 23845 Borstel, Germany

People involved

Ms. Janina Louisa Nandy (PhD fellow sponsored by the PRC) - Research Center Borstel

Abstract

Antimicrobial resistance is one of the major challenges for the 21st century. There is an urgent need on the one hand for new alternative compounds and on the other hand for platforms for compound identification and analysis. The aim of this project is the development of an innovative microfluidic platform that allows time- and cost-efficient evaluation of antimicrobial compounds. This includes (i) the development of microfluidic chips where lipid liposomes can be immobilized and analyzed by fluorescence measurements and (ii) the development of microfluidic derived liposomes that are as close as possible to a bacterial envelope as a model system. In parallel to the platform design, (iii) a group of antimicrobial peptides that were designed with a genetic algorithm will be analyzed regarding their membrane interaction. This will provide a total of 480 pre-ranked peptides as perfect test compounds to support the platform development.1)2)3)

Liposomes generated via microfluidics provide high uniformity. Furthermore, the setup allows excellent control of measurement conditions. The platform will thus facilitate the standardization of measurement conditions, which is an essential requirement for compound testing. In conclusion, the project will contribute to the development of novel membrane-active antimicrobial peptides, which are urgently needed as an alternative for antibiotics. Furthermore, a new liposome-based analysis platform for compounds will be available with the perspective to replace a large part of microbiological measurements in compound testing and thus a concrete market potential.

Benefit for the community

(I) The platform we plan to develop will allow membrane-active compounds to be rapidly and cost-effectively screened for drug development. This could replace a part of the microbiological experiments. (II) Model systems for bacterial envelopes will be available for basic research, for example for the synthetic cell approach. (III) We will use the platform to characterize novel antimicrobial peptides that are promising alternatives for antibiotics. This will play a part in addressing the antimicrobial resistance crisis.

Visit the supervisors lab

Contact to Dr. Christian Nehls

References:
1.
Al Nahas K, Fletcher M, Hammond K, Nehls C, Cama J, Ryadnov MG, Keyser UF, 2022
Measuring Thousands of Single-Vesicle Leakage Events Reveals the Mode of Action of Antimicrobial Peptides
Anal. Chem. 94, 9530-9539
2.
Röckendorf N, Nehls C, Gutsmann T, 2022
Design of Membrane Active Peptides Considering Multi-Objective Optimization for Biomedical Application
Membranes 12, 180
3.
Paulowski L, Donoghue A, Nehls C, Groth S, Koistinen M, Hagge SO, Böhling A, Winterhalter M, Gutsmann T, 2020
The Beauty of Asymmetric Membranes: Reconstitution of the Outer Membrane of Gram-Negative Bacteria
Front. Cell Dev. Biol. 8, 586
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