The Pseudomonas aeruginosa outer membrane permeability barrier and how to overcome it.
The intrinsic resistance of P. aeruginosa to most hydrophilic antibiotics can be explained, in part, on the basis of its low outer membrane permeability. Protein F which constitutes the major outer membrane porin protein for the uptake of hydrophilic compounds, is poorly functional. We have demonstrated that less than 1% of the 200,000 or so copies of protein F per cell can form active functional channels. Our working hypothesis is that the species of LPS associated with individual protein F trimers determines whether these trimers adopt a functional conformation. Since low outer membrane permeability constitutes a major problem for the penetration of antibiotics into P. aeruginosa, we have started to search for compounds which permeabilize outer membranes ('permeabilizers') and thus would be potentially synergistic with antibiotics. Eighteen permeabilizer compounds have been discovered and fall into defined chemical groupings including polycations, organic cations and divalent cation chelators.
Hancock
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D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002621:Chemistry; D018272:Porins; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D018272:Porins