Noise analysis of antibiotic permeation through bacterial channels

Ekaterina M. Nestorovich; Christophe Danelon; Mathias Winterhalter; Sergey M. Bezrukov

doi:10.1117/12.500928

30 April 2003 Noise analysis of antibiotic permeation through bacterial channels

Ekaterina M. Nestorovich, Christophe Danelon, Mathias Winterhalter, Sergey M. Bezrukov

Proceedings Volume 5110, Fluctuations and Noise in Biological, Biophysical, and Biomedical Systems; (2003) https://doi.org/10.1117/12.500928
Event: SPIE's First International Symposium on Fluctuations and Noise, 2003, Santa Fe, New Mexico, United States

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.

Citation Download Citation

Ekaterina M. Nestorovich, Christophe Danelon, Mathias Winterhalter, and Sergey M. Bezrukov "Noise analysis of antibiotic permeation through bacterial channels", Proc. SPIE 5110, Fluctuations and Noise in Biological, Biophysical, and Biomedical Systems, (30 April 2003); https://doi.org/10.1117/12.500928

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KEYWORDS

Molecules

Particles

Capillaries

Diffusion

Ions

Molecular interactions

Proteins

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