Trimethoprim, failure to penetrate into Pseudomonas aeruginosa cells

Permeability mutants of Escherichia coli and Pseudomonas aeruginosa demonstrated a significantly higher susceptibility for trimethoprim (TMP). Although the target enzyme of this drug, dihydrofolic acid reductase, expressed about the same activity, it was comparably inhibited by TMP in permeability mutants and in wild-type strains. The weak activity in wild-type strains depends on the decreased uptake.