Heterogeneity of antibiotic resistance in mucoid isolates of Pseudomonas aeruginosa obtained from cystic fibrosis patients: role of outer membrane proteins

Abstract

Mucoid Pseudomonas aeruginosa strains isolated from cystic fibrosis patients are very heterogeneous and include a class which is hypersusceptible to carbenicillin (minimum inhibitory concentration, less than or equal to 1 microgram/ml). Hypersusceptible mucoid P. aeruginosa isolates were found in 12 of 22 cystic fibrosis patients examined. In cystic fibrosis patients having both resistant and hypersusceptible mucoid strains, 24 of 54 mucoid colonies obtained from a sputum sample were found to belong to the hypersusceptible class. In most instances, hypersusceptible and resistant strains isolated from the same sputum sample were indistinguishable, aside from their antibiotic susceptibilities, by classical methods. A particular pair of mucoid isolates (one hypersusceptible and one resistant) was chosen for further study. The hypersusceptibility was not limited to carbenicillin but was found to extend to other penicillins, tetracycline, and trimethoprim but not to the aminoglycosides gentamicin and tobramycin. The hypersusceptibility of the mucoid strain was found to be unrelated to amount or ability to synthesize alginate. The hypersusceptible strain was found to have two additional outer membrane proteins (32,000 and 25,000 daltons) as compared with the resistant strain. The 32,000-dalton protein, termed protein N1, was found to be correlated to the hypersusceptibility phenotype, as all spontaneous mutants of the hypersusceptible mucoid strain which were capable of growing in the presence of 50 microgram of carbenicillin per ml had lost the 32,000-dalton outer membrane protein. The possible origins of the hypersusceptibility phenotype and the implications of the heterogeneity of mucoid P. aeruginosa in the pathogenesis of P. aeruginosa are discussed.