Roles of porin and β-lactamase in β-lactam resistance of pseudomonas aeruginosa

Pseudomonas aeruginosa demonstrates high intrinsic resistance to most β-Iactam antibiotics. Two factors that are interrelated appear to be important in this intrinsic resistance:an inducible, chromosomally encoded type Id β-Iactamase and lowouter-membrane permeability. β-Lactamase-noninducible mutants are supersusceptible to manyp-Iactam agents, whereasconstitutively derepressed mutants are considerably more resistantevento so-called β-Iactamase-stable β-Iactams. For the latter mutants, by analysis of kinetics, it can be demonstrated that synergybetweenslowpermeation across the outer membrane and slow hydrolysisof the β-Iactamase-stable β-Iactams can explain resistance. Wild-type P. aeruginosa allows outer membrane permeation of β-Iactam 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 β-Iactam antibiotics. Nevertheless, this porin is apparently a conduit for β-Iactams, since protein F-deficient mutants have small changes in susceptibility to certain β-Iactam agents. This low outermembrane permeability acting in synergy with β-Iactamase is probably responsible for intrinsic β-Iactam resistance in P. aeruginosa.