Roles of porin and beta-lactamase in beta-lactam resistance of Pseudomonas aeruginosa.
Pseudomonas aeruginosa demonstrates high intrinsic resistance to most beta-lactam antibiotics. Two factors that are interrelated appear to be important in this intrinsic resistance: an inducible, chromosomally encoded type Id beta-lactamase and low outer-membrane permeability. beta-Lactamase-noninducible mutants are supersusceptible to many beta-lactam agents, whereas constitutively derepressed mutants are considerably more resistant even to so-called beta-lactamase-stable beta-lactams. For the latter mutants, by analysis of kinetics, it can be demonstrated that synergy between slow permeation across the outer membrane and slow hydrolysis of the beta-lactamase-stable beta-lactams can explain resistance. Wild-type P. aeruginosa allows outer membrane permeation of beta-lactam agents at rates 1%-8% of those measured for Escherichia coli. The majority of trans-outer-membrane channels formed by P. aeruginosa porin protein F are too small to allow passage of beta-lactam antibiotics. Nevertheless, this porin is apparently a conduit for beta-lactams, since protein F-deficient mutants have small changes in susceptibility to certain beta-lactam agents. This low outer-membrane permeability acting in synergy with beta-lactamase is probably responsible for intrinsic beta-lactam resistance in P. aeruginosa.
Hancock
R E
RE
Department of Microbiology, University of British Columbia, Vancouver, Canada.
Woodruff
W A
WA
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D007473:Ion Channels / Q000378:metabolism; D018272:Porins; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D007473:Ion Channels; D018272:Porins; D047090:beta-Lactams; D001618:beta-Lactamases