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An Outer Membrane Vesicle-Based Permeation Assay (OMPA) for Assessing Bacterial Bioavailability

  • When searching for new antibiotics against Gram-negative bacterial infections, a better understanding of the permeability across the cell envelope and tools to discriminate high from low bacterial bioavailability compounds are urgently needed. Inspired by the phospholipid vesicle-based permeation assay (PVPA), which is designed to predict non-facilitated permeation across phospholipid membranes, outer membrane vesicles (OMVs) of Escherichia coli either enriched or deficient of porins are employed to coat filter supports for predicting drug uptake across the complex cell envelope. OMVs and the obtained in vitro model are structurally and functionally characterized using cryo-TEM, SEM, CLSM, SAXS, and light scattering techniques. In vitro permeability, obtained from the membrane model for a set of nine antibiotics, correlates with reported in bacterio accumulation data and allows to discriminate high from low accumulating antibiotics. In contrast, the correlation of the same data set generated by liposome-based comparator membranes is poor. This better correlation of the OMV-derived membranes points to the importance of hydrophilic membrane components, such as lipopolysaccharides and porins, since those features are lacking in liposomal comparator membranes. This approach can offer in the future a high throughput screening tool with high predictive capacity or can help to identify compound- and bacteria-specific passive uptake pathways.

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Document Type:Article
Author:Robert RichterORCiD, Mohamed A. M. KamalORCiD, Marcus Koch, Bart-Jan NiebuurORCiD, Anna-Lena Huber, Adriely GoesORCiD, Carsten VolzORCiD, Julia VergalliORCiD, Tobias KrausORCiD, Rolf MüllerORCiD, Nicole Schneider-DaumORCiD, Gregor FuhrmannORCiD, Jean-Marie PagèsORCiD, Claus-Michael LehrORCiD
Parent Title (English):Advanced Healthcare Materials
First Page:2101180
Date of Publication (online):2021/10/06
Year of first Publication:2022
Release Date:2022/05/23
Tag:antimicrobial resistance; bacterial bioavailability; drug optimization; extracellular vesicles; in vitro studies
Impact:11.092 (2021)
Funding Information:Helmholtz Research Program “Infection Research”
Groups:Physikalische Analytik
DDC classes:500 Naturwissenschaften und Mathematik / 570 Biowissenschaften, Biologie
Open Access:Open Access
Signature:INM 2022/010
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International