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

Abstract

SUMMARY. Reduced cell permeability and target penicillin-binding protein modification were investigated as mechanisms of intrinsic resistance in strains of Pseudomonas aeruginosa resistant to carbenicillin (MIC > 128 mg/L) independently of p-lactamase production. The carbenicillin-resistant strains were also remarkably resistant to other P-lactams, quinolones, tetracyline and chloramphenicol, whereas carbenicillin-hypersusceptible strains (MIC < 2 mg/L) were very sensitive to these antimicrobial compounds. These observations suggested a non-specific mechanism of resistance involving reduced permeability of the outer layers of the bacterial cell. However, carbenicillin-resistant and carbenicillin-sensitive strains had identical porin levels and the target penicillin-binding proteins of carbenicillin-resistant (MIC 256-2048 mg/L), carbenicillin-sensitive (MIC 64 mg/L) and carbenicillin-hypersusceptible (MIC 0.01 5 mg/L) strains were equally sensitive to p-lactams. Thus, subtle changes in porin function or additional outer-membrane barriers regulating permeability may be involved in intrinsic resistance.

Physiological studies of the regulation of beta-lactamase expression in Pseudomonas maltophilia

“…Pseudomonads cause infections, e.g., in immunocompromised patients, that are difficult to treat. The high natural resistance of these pathogens against ,-lactams is based on their low outer membrane permeability (5,7,11,13,15; R. G. Hewinson, M. P. E. Slack, and W. W. Nichols, in J. Ishigami, ed., Recent Advances in Chemotherapy, Proc. 14th Int.…”

Dissociation of surface properties and "intrinsic" resistance to lactams in Pseudomonas aeruginosa

“…Tnvolvement of B lactamase in their resistance had been discounted previously (Williams et ai., 1984b). A similar cross-resistance profile is observed in naZB laboratory mutants obtained under selection pressure with nalidixic acid (Rella and Haas, 1982) and a cross-hypersusceptibility to tetracyclines, chloramphenicol and quinolones is observed in some carbenicillin-hypersusceptible strains (Noguchi et al, 1980;Livermore, 1984). It seems unlikely that any specific target modification simultaneously could modulate susceptibility to such a range of diverse chemicals.…”

“…Represen tat ive in trinsicall y-resis tan t strains later were shown to have penicillin-binding proteins with unaltered affinity for p lactams, and it was suggested that their insensitivity may have been due to reduced permeability. This was not determined by decreased porin expression (Livermore, 1984) but may have reflected porin regulation by other outer-membrane components such as the LPS. We therefore examined LPS-related surface properties in large groups of distinct carbenicillinresistant and -sensitive P. aeruginosa strains for possible relationships to antibiogram.…”

“…In P . aeruginosa, however, the amount of porin protein is surprisingly large considering the low permeability of the organism (Angus et al, 1982;Hancock, 1984), and is undiminished in intrinsically-resistant strains (Livermore, 1984). To accommodate these observations, it is postulated that porin function in P. aeruginosa may be controlled by other outermembrane components including the lipopolysaccharide (LPS) (Angus et al, 1982;Kropinski et al, 1982).…”

Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction

“…Unfortunately, selection of the most appropriate antibiotic is complicated due to the ability of P. aeruginosa to develop resistance to multiple classes of antibiotics. Pseudomonas aeruginosa can develop resistance to antibacterial because of the low permeability of its outer membrane (Livermore 1984), the constitutive expression of various efflux pumps (Livermore 2001) and the naturally occurring chromosomal AmpC b-lactamase, giving it sensitivity towards penicillin G; aminopenicillins, first and second generation cephalosporins (Nordmann and Guibert 1998). Pseduomonas aeruginosa easily acquires additional resistance mechanisms, which leads to serious therapeutic problems (Micek, Lloyd et al 2005).…”