Decreased outer membrane permeability in imipenem-resistant mutants of Pseudomonas aeruginosa

The outer membrane of imipenem-resistant mutants of Pseudomonas aeruginosa was shown to have decreased permeability to imipenem but not to cephaloridine. These experiments were performed with intact cells and liposomes containing imipenem-hydrolyzing beta-lactamase derived from Pseudomonas maltophilia, in both cases utilizing an imipenem concentration of 50 microM. In contrast, liposome swelling assays using imipenem at 8 mM detected no significant difference between the imipenem-resistant mutants and their parents. It was found that the outer membrane of P. aeruginosa has a saturable specific channel through which imipenem travels mainly at low concentrations, whereas at high concentrations this pathway is obscured by diffusion through nonspecific porin channels.