Carbenicillin resistance of Pseudomonas aeruginosa

Abstract

Four strains of Pseudomonas aeruginosa obtained from clinical isolates which are carbenicillin resistant were studied to find the cause(s) of resistance to this beta-lactam antibiotic. The electrophoresis patterns of the four strains (PH20610, PH20815, PH4011, and PH4301) were found to be different from those of a wild-type strain, P. aeruginosa NCTC 10662, and appeared to lack penicillin-binding protein 2. Affinity of other penicillin-binding proteins from strains PH20610 and PH20815 for carbenicillin seemed to be normal or slightly diminished. Electrophoretic patterns of penicillin-binding proteins from strains PH4011 and PH4301 had more profound differences, since the affinities of their penicillin-binding proteins 1a, 1b, and 4 for carbenicillin were decreased by nearly two orders of magnitude relative to the preparations from the wild-type strain. Kinetic studies on binding of carbenicillin to penicillin-binding proteins both in isolated membrane preparations and in intact cells revealed that carbenicillin penetration into resistant cells was a much slower process than in susceptible cells, suggesting that the outer envelope structures serve as an efficient barrier against carbenicillin entry into our P. aeruginosa strains from clinical isolates.

Correlation between lipopolysaccharide structure and permeability resistance in beta-lactam-resistant Pseudomonas aeruginosa

“…Permeability barriers to P-lactam antibiotics have been observed in clinical isolates of P. aeruginosa (23). The specific changes within the clinical isolates are unknown.…”

“…The outer membrane of Pseudomonas aeruginosa has long been considered a barrier against ,B-lactam antibiotics (5,23,24). These compounds are believed to permeate through hydrophilic pores in the membrane (10).…”

“…This correlation did not hold for penam derivatives, with the lower-molecular-weight, dianionic molecules being the most effective. Mutants of this type were changed in the amount of "side chain" sugars or, to a minor extent, in their outer membrane protein profiles.The outer membrane of Pseudomonas aeruginosa has long been considered a barrier against ,B-lactam antibiotics (5,23,24). These compounds are believed to permeate through hydrophilic pores in the membrane (10).…”

Lipopolysaccharide Alterations Responsible for Combined Quinolone and β-Lactam Resistance in <i>Pseudomonas aeruginosa</i>

“…The cell envelope was considered responsible for carbenicillin resis tance almost a decade ago [30]. Hancock et al [13] provided evidence for the interplay be- tween LPS and porin F: only a few protein F molecules form active functional channels in vivo and the state of LPS is able to influence the number of open functional protein F pores in the outer membrane [18,26].…”

Penicillin-Binding Proteins, Porins Andouter-Membrane Permeability of Carbenicillin-Resistant and -Susceptible Strains of Pseudomonas Aeruginosa

“…Various modifications of the target penicillin-binding proteins (PBPs) have been shown to be associated with carbenicillin resistance in P . aeruginosa (Curtis et al, 1978;Mirelman, Nuchamowitz, and Rubinstein, 198 1;Godfrey, Bryan and Rabin, 1981;Rodriguez-Tebar et al, 1982); nevertheless secondary defences including p-lactamase synthesis and impermeability were also implicated in some of the strains described by these authors.…”