Bacterial Membrane, a Key for Controlling Drug Influx and Efflux (original) (raw)

Targets, Mechanisms and Resistance, 2013

Abstract

ABSTRACT The worldwide dissemination of resistant bacteria has severely reduced the efficacy of our antibiotic arsenal and increased the frequency of therapeutic failure. Modifications of membrane permeability by changing the expression of transporters alter the mechanical barrier to control the intracellular concentration of antibiotics. This first line of bacterial defense actively participates in the dissemination of multidrug-resistance phenotype.The regulation of membrane permeability and the expression of appropriate channel-forming proteins such as porins or efflux pumps is a key way controlling the intracellular concentration of β-lactams and quinolones, two prominent classes of our antibiotic arsenal. It is necessary to decipher functional, structural, and genetic aspects of the membrane transporters to understand their involvement in membrane physiology and permeability. Regarding the clinical aspect, resistant bacterial strains exhibit significant variations in transporters' expression under antibiotic pressure, demonstrating their role in the adaptation of membrane permeability.Faced with bacterial membrane adaptation, a number of scientific challenges address the drug influx and efflux in resistant isolates. By what means can we circumvent the bacterial membrane controls and bypass the barrier: by using permeabilizers and increasing the influx rate? How can we submerge the efflux activity: by synthesizing efflux blockers? Several studies carried out in these large areas have provided information for the development of a new generation of antibacterial agents exhibiting a variety of chemical–biological properties. Consequently, different chemical or natural groups of modulators of the bacterial membrane permeability have been characterized to increase the intracellular concentration of antibiotics as “escort or adjuvant” molecules. Used in combination, they can restore the activity of old antibiotics in multidrug-resistant gram-negative bacteria.

Jean-marie Pagès hasn't uploaded this paper.

Let Jean-marie know you want this paper to be uploaded.

Ask for this paper to be uploaded.