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Kanamycin Uptake into E. Coli Is Facilitated by OmpF and OmpC Porin Channels Located in the Outer Membrane

preprint
submitted on 07.02.2020 and posted on 10.02.2020 by Jayesh Arun Bafna, Eulàlia Sans-Serramitjana, Silvia Acosta-Gutiérrez, Igor Bodrenko, Daniel Hörömpöli, Anne Berscheid, Heike Brötz-Oesterhelt, Mathias Winterhalter, Matteo Ceccarelli

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 E. 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 mM 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.

Funding

Innovative Medicines Initiative Joint Undertaking under Grant Agreement no. 115525

European Union's seventh framework programme (FP7/2007-2013) and EFPIA companies

Translocation consortium (www.translocation.com) and has received support from the Innovative Medicines Initiative Joint Undertaking under Grant Agreement no. 115525

German Center of Infection Research (DZIF), project TTU 09.819

Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy – EXC 2124 – 390838134.

History

Email Address of Submitting Author

j.bafna@jacobs-university.de

Institution

Jacobs University

Country

Germany

ORCID For Submitting Author

0000-0002-4192-1573

Declaration of Conflict of Interest

No Conflict of Interest

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