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Proceedings Paper

Noise analysis of antibiotic permeation through bacterial channels
Author(s): Ekaterina M. Nestorovich; Christophe Danelon; Mathias Winterhalter; Sergey M. Bezrukov
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Paper Abstract

Statistical analysis of high-resolution current recordings from a single ion channel reconstituted into a planar lipid membrane allows us to study transport of antibiotics at the molecular detail. Working with the general bacterial porin, OmpF, we demonstrate that addition of zwitterionic β-lactam antibiotics to the membrane-bathing solution introduces transient interruptions in the small-ion current through the channel. Time-resolved measurements reveal that one antibiotic molecule blocks one of the monomers in the OmpF trimer for characteristic times from microseconds to hundreds of microseconds. Spectral noise analysis enables us to perform measurements over a wide range of changing parameters. In all cases studied, the residence time of an antibiotic molecule in the channel exceeds the estimated time for free diffusion by orders of magnitude. This demonstrates that, in analogy to substrate-specific channels that evolved to bind specific metabolite molecules, antibiotics have 'evolved' to be channel-specific. The charge distribution of an efficient antibiotic complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a zone of attraction inside the channel and compensates the penetrating molecule's entropy loss and desolvation energy. This facilitates antibiotic translocation through the narrowest part of the channel and accounts for higher antibiotic permeability rates.

Paper Details

Date Published: 30 April 2003
PDF: 6 pages
Proc. SPIE 5110, Fluctuations and Noise in Biological, Biophysical, and Biomedical Systems, (30 April 2003); doi: 10.1117/12.500928
Show Author Affiliations
Ekaterina M. Nestorovich, National Institutes of Health (United States)
Christophe Danelon, Institut Pharmacologie et Biologie Structurale (France)
Mathias Winterhalter, Institut Pharmacologie et Biologie Structurale (France)
Sergey M. Bezrukov, National Institutes of Health (United States)


Published in SPIE Proceedings Vol. 5110:
Fluctuations and Noise in Biological, Biophysical, and Biomedical Systems
Sergey M. Bezrukov; Hans Frauenfelder; Frank Moss, Editor(s)

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