Abstract
On the basis of a simple theoretical model, the ease of penetration of β-lactam antibiotics through the outer membrane of Escherichia coli was measured. The cell envelope was found to act as a diffusion barrier to both penicillins and cephalosporins. The validity of the model and the cooperative action of cell-bound β-lactamase and outer membrane were further verified by comparing calculated and experimentally determined velocities of β-lactam hydrolysis by intact cells and sonically treated cell suspensions. The results showed good correspondence at five different antibiotic concentrations. Similar conclusions could be drawn from a comparison of β-lactam concentrations on both sides of the outer membrane, calculated from enzyme kinetic measurements and minimal inhibitory concentrations for both a β-lactamase-producing E. coli and its enzyme-negative variant. in the case of benzylpenicillin and cephalothin, however, no correspondence was found. The joint action of several parameters determining the efficacy of penicillins and cephalosporins against β-lactamase-producing E. coli is discussed.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boman H. G., Nordström K., Normark S. Penicillin resistance in Escherichia coli K12: synergism between penicillinases and a barrier in the outer part of the envelope. Ann N Y Acad Sci. 1974 May 10;235(0):569–586. doi: 10.1111/j.1749-6632.1974.tb43291.x. [DOI] [PubMed] [Google Scholar]
- Burman L. G., Nordström K., Bloom G. D. Murein and the outer penetration barrier of Escherichia coli K-12, Proteus mirabilis, and Pseudomonas aeruginosa. J Bacteriol. 1972 Dec;112(3):1364–1374. doi: 10.1128/jb.112.3.1364-1374.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Costerton J. W., Cheng K. J. The role of the bacterial cell envelope in antibiotic resistance. J Antimicrob Chemother. 1975 Dec;1(4):363–377. doi: 10.1093/jac/1.4.363. [DOI] [PubMed] [Google Scholar]
- Datta N., Kontomichalou P. Penicillinase synthesis controlled by infectious R factors in Enterobacteriaceae. Nature. 1965 Oct 16;208(5007):239–241. doi: 10.1038/208239a0. [DOI] [PubMed] [Google Scholar]
- Hamilton-Miller J. M., Smith J. T., Knox R. Interaction of cephaloridine with penicillinase-producing gram-negative bacteria. Nature. 1965 Oct 16;208(5007):235–237. doi: 10.1038/208235a0. [DOI] [PubMed] [Google Scholar]
- Hamilton-miller J. M. Use of Michaelis-Menten kinetics in the analysis of synergism between beta-lactam antibiotics. J Theor Biol. 1971 May;31(2):171–176. doi: 10.1016/0022-5193(71)90181-0. [DOI] [PubMed] [Google Scholar]
- Jack G. W., Richmond M. H. A comparative study of eight distinct beta-lactamases synthesized by gram-negative bacteria. J Gen Microbiol. 1970 Apr;61(1):43–61. doi: 10.1099/00221287-61-1-43. [DOI] [PubMed] [Google Scholar]
- NOVICK R. P. Micro-iodometric assay for penicillinase. Biochem J. 1962 May;83:236–240. doi: 10.1042/bj0830236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neu H. C., Chou J. Release of surface enzymes in Enterobacteriaceae by osmotic shock. J Bacteriol. 1967 Dec;94(6):1934–1945. doi: 10.1128/jb.94.6.1934-1945.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neu H. C. The surface localization of penicillinases in Escherichia coli and Salmonella typhimurium. Biochem Biophys Res Commun. 1968 Jul 26;32(2):258–263. doi: 10.1016/0006-291x(68)90378-1. [DOI] [PubMed] [Google Scholar]
- Nikaido H. Outer membrane of Salmonella typhimurium. Transmembrane diffusion of some hydrophobic substances. Biochim Biophys Acta. 1976 Apr 16;433(1):118–132. doi: 10.1016/0005-2736(76)90182-6. [DOI] [PubMed] [Google Scholar]
- Osborn M. J., Gander J. E., Parisi E., Carson J. Mechanism of assembly of the outer membrane of Salmonella typhimurium. Isolation and characterization of cytoplasmic and outer membrane. J Biol Chem. 1972 Jun 25;247(12):3962–3972. [PubMed] [Google Scholar]
- Richmond M. H., Jack G. W., Sykes R. B. Mechanisms of drug resistance. The beta-lactamases of gram-negative bacteria including pseudomonads. Ann N Y Acad Sci. 1971 Jun 11;182:243–257. doi: 10.1111/j.1749-6632.1971.tb30661.x. [DOI] [PubMed] [Google Scholar]
- SMITH J. T., HAMILTON-MILLER J. M. Differences between pencillinases from gram-positive and gram-negative bacteria. Nature. 1963 Mar 9;197:976–978. doi: 10.1038/197976a0. [DOI] [PubMed] [Google Scholar]
- Smith J. T., Hamilton-Miller J. M., Knox R. Bacterial resistance to penicillins and cephalosporins. J Pharm Pharmacol. 1969 Jun;21(6):337–358. doi: 10.1111/j.2042-7158.1969.tb08267.x. [DOI] [PubMed] [Google Scholar]
- Sykes R. B., Matthew M. The beta-lactamases of gram-negative bacteria and their role in resistance to beta-lactam antibiotics. J Antimicrob Chemother. 1976 Jun;2(2):115–157. doi: 10.1093/jac/2.2.115. [DOI] [PubMed] [Google Scholar]
