Caister Academic Press

The Permeability Barrier: Passive and Active Drug Passage Across Membranes

Kozhinjampara R Mahendran, Robert Schulz, Helge Weingart, Ulrich Kleinekathöfer and Mathias Winterhalter
from: Bacterial Membranes: Structural and Molecular Biology (Edited by: Han Remaut and Rémi Fronzes). Caister Academic Press, U.K. (2014)

Abstract

Under antibiotic stress a reduced permeability for drugs to enter and an enhanced active extrusion of undesired compounds was observed in Gram-negative bacteria. With respect to the influx of drugs the first line of defense is the outer membrane containing a number of channel forming proteins called porins allowing passive penetration of water-soluble compounds into the periplasmic space. Mutations in the constriction zone or a reduction of the number of porins reduce the flux. In addition porins coupled to efflux pumps allow the cell to eject antibiotics actively into the extracellular space. In order to understand the function of the involved proteins, a quantification of the individual transport elements is necessary. Here we describe experimental and computational biophysical methods to characterize molecular transport of antibiotics and small compounds across bacterial membranes read more ...
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