Abstract
Pseudomonas aeruginosa K 799/WT and a mutant of this strain, P. aeruginosa K 799/61 ("mutant 61"), that is very sensitive to most beta-lactam antibiotics tested were used to assess the importance of penetration barriers in the resistance of P. aeruginosa to penicillins and cephalosporins. The affinities of various beta-lactams to the penicillin-binding proteins found in membranes prepared from both strains were compared by measuring their competition for the binding of benzyl[14C] penicillin to each of these proteins. Only minor differences between the wild type and the mutant 61 were found. The high sensitivity of the mutant therefore cannot be attributed to drastic alterations of these target proteins, nor can the resistance of the wild type be ascribed to penicillin-binding proteins with low affinities for beta-lactams. Experiments in which the ease of penetration of beta-lactams into the penicillin-binding proteins was measured with exponentially growing intact cells instead of membranes, however, clearly demonstrated an easy access of beta-lactam antibiotics to these proteins in the mutant and an efficient exclusion from the same targets in the wild type.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blumberg P. M., Strominger J. L. Interaction of penicillin with the bacterial cell: penicillin-binding proteins and penicillin-sensitive enzymes. Bacteriol Rev. 1974 Sep;38(3):291–335. doi: 10.1128/br.38.3.291-335.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Curtis N. A., Brown C., Boxall M., Boulton M. G. Inhibition of Escherichia coli K-12 by beta-lactam antibiotics with poor antibacterial activity: interaction of permeability and intrinsic activity against penicillin-binding proteins. Antimicrob Agents Chemother. 1979 Mar;15(3):332–336. doi: 10.1128/aac.15.3.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Curtis N. A., Orr D., Ross G. W., Boulton M. G. Competition of beta-lactam antibiotics for the penicillin-binding proteins of Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella aerogenes, Proteus rettgeri, and Escherichia coli: comparison with antibacterial activity and effects upon bacterial morphology. Antimicrob Agents Chemother. 1979 Sep;16(3):325–328. doi: 10.1128/aac.16.3.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ericsson H. M., Sherris J. C. Antibiotic sensitivity testing. Report of an international collaborative study. Acta Pathol Microbiol Scand B Microbiol Immunol. 1971;217(Suppl):1+–1+. [PubMed] [Google Scholar]
- Laemmli U. K., Favre M. Maturation of the head of bacteriophage T4. I. DNA packaging events. J Mol Biol. 1973 Nov 15;80(4):575–599. doi: 10.1016/0022-2836(73)90198-8. [DOI] [PubMed] [Google Scholar]
- Mills B. J., Holloway B. W. Mutants of Pseudomonas aeruginosa that show specific hypersensitivity to aminoglycosides. Antimicrob Agents Chemother. 1976 Sep;10(3):411–416. doi: 10.1128/aac.10.3.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richmond M. H., Clark D. C., Wotton S. Indirect method for assessing the penetration of beta-lactamase-nonsusceptible penicillins and cephalosporins in Escherichia coli strains. Antimicrob Agents Chemother. 1976 Aug;10(2):215–218. doi: 10.1128/aac.10.2.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spratt B. G. Properties of the penicillin-binding proteins of Escherichia coli K12,. Eur J Biochem. 1977 Jan;72(2):341–352. doi: 10.1111/j.1432-1033.1977.tb11258.x. [DOI] [PubMed] [Google Scholar]
- Tsuchiya K., Kondo M., Nagatomo H. SCE-129, antipseudomonal cephalosporin: in vitro and in vivo antibacterial activities. Antimicrob Agents Chemother. 1978 Feb;13(2):137–145. doi: 10.1128/aac.13.2.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmermann W. Penetration through the gram-negative cell wall: a co-determinant of the efficacy of beta-lactam antibiotics. Int J Clin Pharmacol Biopharm. 1979 Mar;17(3):131–134. [PubMed] [Google Scholar]