Selfinduced Uptake Of Aminoglycoside Antibiotics Through The Outer Membrane Of Gramnegative Bacteria

Polycationic antibiotics can traverse the outer membrane by means other than diffusion through pores. As originally outlined by Hancock [2,11,12], aminoglycoside antibiotics such as tobramycin and gentamicin enter Gram-negative bacteria by a self-promoted pathway, involving disruption of LPS-Mg++ cross bridges, which as indicated above pose the major barrier to antibiotic entry. Disruption depends on the cationic structure of aminoglycosides, can be effected by other polycations such as polymyxin and protamine, and is mechanistically dependent on displacement of Mg++ from cross bridges. The resulting rearrangement of LPS and exposure of the OM bilayer provides sufficient localized destabilization of the bilayer to allow entry of aminoglycoside to the periplasm. Bacterial species such as Burkholderia cepacia, which have LPS with a low phosphate and high arabinosamine content, are resistant to polycationic antibiotics, apparently because the B. cepacia LPS does not bind polycations effectively [13]. The general phenomenon of self-induced uptake is discussed by Hancock [5] in the context of modification of outer membrane permeability for enhancement of antibiotic efficacy.

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