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High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB. / Bartsch, A.; Llabrés, S.; Pein, F. et al.
In: Scientific Reports, Vol. 9, 1264, 04.02.2019.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Bartsch, A, Llabrés, S, Pein, F, Kattner, C, Schön, M, Diehn, M, Tanabe, M, Munk, A, Zachariae, U & Steinem, C 2019, 'High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB', Scientific Reports, vol. 9, 1264. https://doi.org/10.1038/s41598-018-37066-9

APA

Bartsch, A., Llabrés, S., Pein, F., Kattner, C., Schön, M., Diehn, M., Tanabe, M., Munk, A., Zachariae, U., & Steinem, C. (2019). High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB. Scientific Reports, 9, Article 1264. https://doi.org/10.1038/s41598-018-37066-9

Vancouver

Bartsch A, Llabrés S, Pein F, Kattner C, Schön M, Diehn M et al. High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB. Scientific Reports. 2019 Feb 4;9:1264. doi: 10.1038/s41598-018-37066-9

Author

Bartsch, A. ; Llabrés, S. ; Pein, F. et al. / High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB. In: Scientific Reports. 2019 ; Vol. 9.

Bibtex

@article{af1fb97902ae4dbdaf87dea8451f4aaa,
title = "High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB",
abstract = "The permeation of most antibiotics through the outer membrane of Gram-negative bacteria occurs through porin channels. To design drugs with increased activity against Gram-negative bacteria in the face of the antibiotic resistance crisis, the strict constraints on the physicochemical properties of the permeants imposed by these channels must be better understood. Here we show that a combination of high-resolution electrophysiology, new noise-filtering analysis protocols and atomistic biomolecular simulations reveals weak binding events between the β-lactam antibiotic ampicillin and the porin PorB from the pathogenic bacterium Neisseria meningitidis. In particular, an asymmetry often seen in the electrophysiological characteristics of ligand-bound channels is utilised to characterise the binding site and molecular interactions in detail, based on the principles of electro-osmotic flow through the channel. Our results provide a rationale for the determinants that govern the binding and permeation of zwitterionic antibiotics in porin channels.",
author = "A. Bartsch and S. Llabr{\'e}s and F. Pein and C. Kattner and M. Sch{\"o}n and M. Diehn and M. Tanabe and A. Munk and U. Zachariae and C. Steinem",
year = "2019",
month = feb,
day = "4",
doi = "10.1038/s41598-018-37066-9",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB

AU - Bartsch, A.

AU - Llabrés, S.

AU - Pein, F.

AU - Kattner, C.

AU - Schön, M.

AU - Diehn, M.

AU - Tanabe, M.

AU - Munk, A.

AU - Zachariae, U.

AU - Steinem, C.

PY - 2019/2/4

Y1 - 2019/2/4

N2 - The permeation of most antibiotics through the outer membrane of Gram-negative bacteria occurs through porin channels. To design drugs with increased activity against Gram-negative bacteria in the face of the antibiotic resistance crisis, the strict constraints on the physicochemical properties of the permeants imposed by these channels must be better understood. Here we show that a combination of high-resolution electrophysiology, new noise-filtering analysis protocols and atomistic biomolecular simulations reveals weak binding events between the β-lactam antibiotic ampicillin and the porin PorB from the pathogenic bacterium Neisseria meningitidis. In particular, an asymmetry often seen in the electrophysiological characteristics of ligand-bound channels is utilised to characterise the binding site and molecular interactions in detail, based on the principles of electro-osmotic flow through the channel. Our results provide a rationale for the determinants that govern the binding and permeation of zwitterionic antibiotics in porin channels.

AB - The permeation of most antibiotics through the outer membrane of Gram-negative bacteria occurs through porin channels. To design drugs with increased activity against Gram-negative bacteria in the face of the antibiotic resistance crisis, the strict constraints on the physicochemical properties of the permeants imposed by these channels must be better understood. Here we show that a combination of high-resolution electrophysiology, new noise-filtering analysis protocols and atomistic biomolecular simulations reveals weak binding events between the β-lactam antibiotic ampicillin and the porin PorB from the pathogenic bacterium Neisseria meningitidis. In particular, an asymmetry often seen in the electrophysiological characteristics of ligand-bound channels is utilised to characterise the binding site and molecular interactions in detail, based on the principles of electro-osmotic flow through the channel. Our results provide a rationale for the determinants that govern the binding and permeation of zwitterionic antibiotics in porin channels.

U2 - 10.1038/s41598-018-37066-9

DO - 10.1038/s41598-018-37066-9

M3 - Journal article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 1264

ER -