Decreases of the susceptibility to low molecular weight beta-lactam antibiotics in imipenem-resistant Pseudomonas aeruginosa mutants: role of outer membrane protein D2 in their diffusion.
Decreased susceptibilities to two low Mr beta-lactam antibiotics, CS-533 (a carbapenem; Mr, 339) and CGP31608 (a penem; Mr, 262), were found in imipenem-resistant mutants of Pseudomonas aeruginosa PAO. The diffusion rates of several beta-lactam antibiotics including imipenem, CS-533 and CGP31608 across the proteoliposome membrane reconstituted from the outer membrane of the wild type strain or its imipenem-resistant mutants were determined by the liposome swelling technique. Diffusion rates of imipenem, CS-533 and CGP31608 in the proteoliposomes from outer membranes of the imipenem-resistant strain were found to be 27, 20 and 47%, respectively, of the diffusion rates in proteoliposomes reconstituted from outer membranes of the sensitive parent strain. The SDS-polyacrylamide gel electrophoretogram of outer membrane proteins of the imipenem-resistant strains indicated deletion of protein D2. These results suggested that decreased susceptibilities to imipenem, CS-533 and CGP31608 were due to decreased outer membrane permeability, and that D2 is a protein fraction constituting pores for diffusion of these antibiotics through the P. aeruginosa outer membrane.
Gotoh
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N
Department of Microbiology, Kyoto Pharmaceutical University, Japan.
Nishino
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T
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology*; D004058:Diffusion; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D015378:Imipenem / Q000494:pharmacology*; D007769:Lactams; D008081:Liposomes / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D010539:Permeability; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D013845:Thienamycins; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D015780:Carbapenems; D007769:Lactams; D008081:Liposomes; D013845:Thienamycins; D047090:beta-Lactams; C052019:CGP 31608; D015378:Imipenem; C039536:panipenem