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FEBS Lett. 2011 Jun 6;585(11):1682-90. doi: 10.1016/j.febslet.2011.04.054. Epub 2011 May 3.

Strategies for bypassing the membrane barrier in multidrug resistant Gram-negative bacteria.

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UMR-MD1, Transporteurs Membranaires, Chimiorésistance et Drug Design, Facultés de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France.


In Gram-negative bacteria, the envelope is a sophisticated barrier protecting the cell against external toxic compounds. Membrane transporters, e.g., porins or efflux pumps, are main filters regulating the internal accumulation of various hydrophilic molecules. Regarding bacterial susceptibility towards antibacterial agents, membrane permeability is part of the early bacterial defense. The bacterium manages the translocation process, influx and efflux, to control the intracellular concentration of various molecules. Antibiotics and biocides are substrates of these mechanisms and the continuing emergence of multidrug resistant isolates is a growing worldwide health concern. Different strategies could be proposed to bypass the bacterial membrane barrier, comprising influx and efflux mechanisms, in order to restore the activity of antibiotics against resistant bacteria.

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