Berlin 2008 – wissenschaftliches Programm

Bereiche | Tage | Auswahl | Suche | Downloads | Hilfe

BP: Fachverband Biologische Physik

BP 7: Posters I

BP 7.52: Poster

Montag, 25. Februar 2008, 17:00–19:30, Poster A

The effect of antibiotic binding to bacterial membrane proteins on drug accummulation — •Tivadar Mach¹, K R Mahendran¹, Andrey Bessonov¹, Enrico Spiga², Isabel Sousa³, Helge Weingart¹, Paula Gameiro dos Santos³, Matteo Ceccarelli², and Mathias Winterhalter¹ — ¹Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany — ²Università di Cagliari, 09042 Monserrato (CA), Italy — ³Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal

One of the main mechanisms through which bacteria exhibit resistance to antimicrobials is reduced drug accummulation. A change in permeability of the bacterial membrane for highly effective hydrophilic drugs can be effected by resistant bacteria through the modification or abscence of certain transmembrane proteins. We investigate the permeation pathways of several b-lactam and fluoroquinolone antibiotics into the bacterial cell by the reconstitution of a single bacterial porin into an artificial planar lipid bilayer, measuring the binding of antibiotic molecules through the time-resolved modulation of a small-ion current. Combining these conductance results with fluorescence spectroscopy, molecular dynamics simulations and Minimum Inhibitory Concentration assays, we conclude that efficiency of permeation for antimicrobials depends strongly on their association constant with bacterial pores, with the binding energy counteracting the loss of free entropy of the antibiotic confinement in the channel - potentially leading the way to new antibiotic design.