In Vitro Model of the Gram-Negative Bacterial Cell Envelope for Investigation of Anti-Infective Permeation Kinetics

ACS Infectious Diseases
Florian GraefClaus-Michael Lehr

Abstract

The cell envelope of Gram-negative bacteria is a formidable biological barrier, inhibiting the action of antibiotics by impeding their permeation into the intracellular environment. In-depth understanding of permeation through this barrier remains a challenge, despite its critical role in antibiotic activity. We therefore designed a divisible in vitro permeation model of the Gram-negative bacterial cell envelope, mimicking its three essential structural elements, the inner membrane and the periplasmic space as well as the outer membrane, on a Transwell setup. The model was characterized by contemporary imaging techniques and employed to generate reproducible quantitative and time-resolved permeation data for various fluorescent probes and anti-infective molecules of different structure and physicochemical properties. For a set of three fluorescent probes, the permeation through the overall membrane model was found to correlate with in bacterio permeation. Even more interestingly, for a set of six Pseudomonas quorum sensing inhibitors, such permeability data were found to be predictive for their corresponding in bacterio activities. Further exploration of the capabilities of the overall model yielded a correlation between the pe...Continue Reading

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Citations

Nov 25, 2020·Drug Discovery Today·Carlos Victor Montefusco-PereiraClaus-Michael Lehr
Mar 12, 2021·Advanced Drug Delivery Reviews·Henni-Karoliina RopponenClaus-Michael Lehr
Apr 16, 2021·Advanced Drug Delivery Reviews·Robert Richter, Claus-Michael Lehr
May 11, 2021·Frontiers in Bioengineering and Biotechnology·Justus C HorstmannClaus-Michael Lehr
Jul 3, 2018·ACS Infectious Diseases·Ramkumar IyerAlice L Erwin
Nov 30, 2018·Analytical Chemistry·Hans ProchnowMark Brönstrup
Oct 9, 2019·ACS Infectious Diseases·Ricardo J Ferreira, Peter M Kasson
Aug 25, 2021·Nature Reviews. Chemistry·Marcus MiethkeRolf Müller
Oct 7, 2021·Advanced Healthcare Materials·Robert RichterClaus-Michael Lehr

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