beta-Lactam-resistant Pseudomonas aeruginosa with modified penicillin-binding proteins emerging during cystic fibrosis treatment

Abstract

The emergence of ,B-lactam-resistant strains of Pseudomonas aeruginosa in a cystic fibrosis patient treated with high-dose tobramycin and piperacillin was studied. Two serotypes, M and K, were present before treatment and persisted, with changes in their /8-lactam resistance spectra, during treatment. The resistance was correlated with changes in the penicillin-binding proteins (PBPs) in both serotypes. In the low-level-resistant serotype K organism, PBP-3 either was absent or had lost the ability to bind ['4C]penicillin G. Two serotype M strains, one with low-and one with high-level resistance to several antipseudomonal ,8-lactam antibiotics, were isolated at progressively later stages of therapy. Several differences were noted between the PBP patterns of the resistant M and the susceptible M strains. The affinity for ['4C]penicilhin G was reduced in both resistant strains. PBP bands, with the exception of PBP-6 in the most resistant M type, were barely or not detectable at a ['4C]penicillin G concentration of 39 ,ug/ml. The graduated decrease in affinity for [14C]penicillin G was correlated with increasing 16-lactam resistance and with an increase in the quantity of the protein corresponding to PBP-6. The emergence of the low-level-resistant strains midway through, and of the highly resistant strain in the final stages of, the reported treatment strongly suggested that the resistance resulted from mutation in those strains present before treatment selected for by the high-dose piperacillin treatment.

Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate

“…Previous studies have associated resistance to /Mactams with modified PBPs in different clinical isolates of P. aeruginosa (Godfrey, Bryan & Rabin, 1981;Mirelman, Nuchamowitz & Rubinstein, 1981) but these workers did not consider imipenem. In the present investigation autoradiographic data showed an altered interaction of imipenem with PBP-4 in an imipenem-resistant isolate.…”

State of penicillin-binding proteins and requirements for their bactericidal interaction with β-lactam antibiotics in Serratia marcescens highly resistant to extended-spectrum β-lactams

“…In contrast, the highly resistant strain HR differed from the related strain LR and the sensitive strains by a more than twofold higher content of PBP 6. The augmentation of a low molecular mass PBP in highly p-lactam-resistant Pseudomonas aeruginosa (Godfrey et al, 1981), and of PBP 6 in resistant S. marcescens (Gutmann & Chabbert, 1984) has been reported previously. It is not clear how the doubling of the amount of PBP 6, a non-essential PBP in enterobacteria, should contribute to the high p-lactam resistance of strain HR.…”

Absence of penicillin-binding protein 4 from an apparently normal strain of Bacillus subtilis

“…antibiotic resistance or by recovery of resistant mutants from natural sources (10, 16,18,19,22,34,41,43,46). In contrast, the mutant described below was discovered fortuitously; no mnutagenesis or selection was employed, and its PBP defect was completely unexpected.…”