Kanamycin Uptake into Escherichia coli Is Facilitated by OmpF and OmpC Porin Channels Located in the Outer Membrane
- 5 May 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Infectious Diseases
- Vol. 6 (7), 1855-1865
- https://doi.org/10.1021/acsinfecdis.0c00102
Abstract
Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here, we quantified the uptake of kanamycin across the major porin channels OmpF and OmpC present in the outer membrane of Escherichia coli. Our analysis revealed that, despite its relatively large size, about 10 - 20 kanamycin molecules per second permeate through OmpF and OmpC under a 10 μM concentration gradient, whereas OmpN does not allow the passage. Molecular simulations elucidate the uptake mechanism of kanamycin through these porins. Whole-cell studies with a decisive set of E. coli porin mutants provide evidence that translocation of kanamycin via porins is relevant for antibiotic potency.Keywords
Funding Information
- FP7 Health (115525)
- Deutsche Forschungsgemeinschaft (EXC 2124 ? 390838134)
- Deutsches Zentrum f?r Infektionsforschung (TTU 09.819)
- Ministero dell'Istruzione, dell'Universit? e della Ricerca (2015795S5W)
This publication has 51 references indexed in Scilit:
- Altered Antibiotic Transport in OmpC Mutants Isolated from a Series of Clinical Strains of Multi-Drug Resistant E. coliPLOS ONE, 2011
- Effect of xylitol, sodium fluoride and triclosan containing mouth rinse on Streptococcus mutansContemporary Clinical Dentistry, 2011
- Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy MethodPhysical Review Letters, 2008
- Construction of Escherichia coli K‐12 in‐frame, single‐gene knockout mutants: the Keio collectionMolecular Systems Biology, 2006
- Scalable molecular dynamics with NAMDJournal of Computational Chemistry, 2005
- Development and testing of a general amber force fieldJournal of Computational Chemistry, 2004
- A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP modelThe Journal of Physical Chemistry, 1993
- Ionic channels of excitable membranes. Bertil Hille. Sunderland, Ma: Sinauer Associates, 1984Journal of Neuroscience Research, 1985
- Comparison of simple potential functions for simulating liquid waterThe Journal of Chemical Physics, 1983
- Identification of the outer membrane protein of E.coli that produces transmembrane channels in reconstituted vesicle membranesBiochemical and Biophysical Research Communications, 1976