Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Jan;35(1):73–78. doi: 10.1128/aac.35.1.73

Reevaluation of the factors involved in the efficacy of new beta-lactams against Enterobacter cloacae.

F Bellido 1, J C Pechère 1, R E Hancock 1
PMCID: PMC244944  PMID: 2014984

Abstract

The roles of outer membrane permeability, beta-lactamase stability, and inhibition of penicillin-binding proteins in the activity of new beta-lactams against Enterobacter cloacae were reappraised by using several methodological improvements. Outer membrane permeability in intact cells was determined by using a high-pressure liquid chromatography (HPLC)-based technique that avoided certain possible artifacts of the traditional methods. Vmax values were calculated from the numbers of enzyme molecules produced per cell and from catalytic constant (Kcat) values, which were obtained with purified beta-lactamase. Minimal periplasmic antibiotic concentrations needed to inhibit bacterial cell wall synthesis were estimated from the Zimmermann-Rosselet equation. All the beta-lactams tested formed relatively stable complexes with purified beta-lactamase. The antibiotics that exhibited low affinity for beta-lactamase apparently needed higher periplasmic concentrations to inhibit cell wall synthesis, suggesting a possible correlation between the affinity of beta-lactamase and the affinity of penicillin-binding proteins for the new beta-lactams. By using these estimates of outer membrane permeability, beta-lactamase hydrolysis, and cell wall-inhibiting concentrations, MIC could be theoretically predicted to within 1 dilution for five beta-lactams in three isogenic E. cloacae strains with differences in antibiotic susceptibility due to different porin or beta-lactamase contents.

Full text

PDF
73

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bellido F., Pechère J. C., Hancock R. E. Novel method for measurement of outer membrane permeability to new beta-lactams in intact Enterobacter cloacae cells. Antimicrob Agents Chemother. 1991 Jan;35(1):68–72. doi: 10.1128/aac.35.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bellido F., Veuthey C., Blaser J., Bauernfeind A., Pechère J. C. Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate. J Antimicrob Chemother. 1990 Jan;25(1):57–68. doi: 10.1093/jac/25.1.57. [DOI] [PubMed] [Google Scholar]
  3. Bellido F., Vladoïanu I. R., Auckenthaler R., Suter S., Wacker P., Then R. L., Pechère J. C. Permeability and penicillin-binding protein alterations in Salmonella muenchen: stepwise resistance acquired during beta-lactam therapy. Antimicrob Agents Chemother. 1989 Jul;33(7):1113–1115. doi: 10.1128/aac.33.7.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bush K., Freudenberger J. S., Sykes R. B. Interaction of azthreonam and related monobactams with beta-lactamases from gram-negative bacteria. Antimicrob Agents Chemother. 1982 Sep;22(3):414–420. doi: 10.1128/aac.22.3.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bush K., Tanaka S. K., Bonner D. P., Sykes R. B. Resistance caused by decreased penetration of beta-lactam antibiotics into Enterobacter cloacae. Antimicrob Agents Chemother. 1985 Apr;27(4):555–560. doi: 10.1128/aac.27.4.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cartwright S. J., Waley S. G. Purification of beta-lactamases by affinity chromatography on phenylboronic acid-agarose. Biochem J. 1984 Jul 15;221(2):505–512. doi: 10.1042/bj2210505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Charnas R. L., Then R. L. Mechanism of inhibition of chromosomal beta-lactamases by third-generation cephalosporins. Rev Infect Dis. 1988 Jul-Aug;10(4):752–760. doi: 10.1093/clinids/10.4.752. [DOI] [PubMed] [Google Scholar]
  8. Frère J. M., Joris B. Penicillin-sensitive enzymes in peptidoglycan biosynthesis. Crit Rev Microbiol. 1985;11(4):299–396. doi: 10.3109/10408418409105906. [DOI] [PubMed] [Google Scholar]
  9. Gutmann L., Williamson R. A model system to demonstrate that beta-lactamase-associated antibiotic trapping could be a potential means of resistance. J Infect Dis. 1983 Aug;148(2):316–321. doi: 10.1093/infdis/148.2.316. [DOI] [PubMed] [Google Scholar]
  10. Hashizume T., Ishino F., Nakagawa J., Tamaki S., Matsuhashi M. Studies on the mechanism of action of imipenem (N-formimidoylthienamycin) in vitro: binding to the penicillin-binding proteins (PBPs) in Escherichia coli and Pseudomonas aeruginosa, and inhibition of enzyme activities due to the PBPs in E. coli. J Antibiot (Tokyo) 1984 Apr;37(4):394–400. doi: 10.7164/antibiotics.37.394. [DOI] [PubMed] [Google Scholar]
  11. Hiraoka M., Masuyoshi S., Mitsuhashi S., Tomatsu K., Inoue M. Cephalosporinase interactions and antimicrobial activity of BMY-28142, ceftazidime and cefotaxime. J Antibiot (Tokyo) 1988 Jan;41(1):86–93. doi: 10.7164/antibiotics.41.86. [DOI] [PubMed] [Google Scholar]
  12. Kobayashi S., Arai S., Hayashi S., Fujimoto K. Beta-lactamase stability of cefpirome (HR 810), a new cephalosporin with a broad antimicrobial spectrum. Antimicrob Agents Chemother. 1986 Nov;30(5):713–718. doi: 10.1128/aac.30.5.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lampe M. F., Allan B. J., Minshew B. H., Sherris J. C. Mutational enzymatic resistance of Enterobacter species to beta-lactam antibiotics. Antimicrob Agents Chemother. 1982 Apr;21(4):655–660. doi: 10.1128/aac.21.4.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Livermore D. M. Do beta-lactamases 'trap' cephalosporins? J Antimicrob Chemother. 1985 May;15(5):511–514. doi: 10.1093/jac/15.5.511. [DOI] [PubMed] [Google Scholar]
  15. Marchou B., Bellido F., Charnas R., Lucain C., Pechère J. C. Contribution of beta-lactamase hydrolysis and outer membrane permeability to ceftriaxone resistance in Enterobacter cloacae. Antimicrob Agents Chemother. 1987 Oct;31(10):1589–1595. doi: 10.1128/aac.31.10.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Minami S., Yotsuji A., Inoue M., Mitsuhashi S. Induction of beta-lactamase by various beta-lactam antibiotics in Enterobacter cloacae. Antimicrob Agents Chemother. 1980 Sep;18(3):382–385. doi: 10.1128/aac.18.3.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nikaido H., Liu W., Rosenberg E. Y. Outer membrane permeability and beta-lactamase stability of dipolar ionic cephalosporins containing methoxyimino substituents. Antimicrob Agents Chemother. 1990 Feb;34(2):337–342. doi: 10.1128/aac.34.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nikaido H., Normark S. Sensitivity of Escherichia coli to various beta-lactams is determined by the interplay of outer membrane permeability and degradation by periplasmic beta-lactamases: a quantitative predictive treatment. Mol Microbiol. 1987 Jul;1(1):29–36. doi: 10.1111/j.1365-2958.1987.tb00523.x. [DOI] [PubMed] [Google Scholar]
  19. Nikaido H., Rosenberg E. Y., Foulds J. Porin channels in Escherichia coli: studies with beta-lactams in intact cells. J Bacteriol. 1983 Jan;153(1):232–240. doi: 10.1128/jb.153.1.232-240.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. POLLOCK M. R. PURIFICATION AND PROPERTIES OF PENICILLINASES FROM TWO STRAINS OF BACILLUS LICHENIFORMIS: A CHEMICAL, PHYSICOCHEMICAL AND PHYSIOLOGICAL COMPARISON. Biochem J. 1965 Mar;94:666–675. doi: 10.1042/bj0940666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Phelps D. J., Carlton D. D., Farrell C. A., Kessler R. E. Affinity of cephalosporins for beta-lactamases as a factor in antibacterial efficacy. Antimicrob Agents Chemother. 1986 May;29(5):845–848. doi: 10.1128/aac.29.5.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Smit J., Kamio Y., Nikaido H. Outer membrane of Salmonella typhimurium: chemical analysis and freeze-fracture studies with lipopolysaccharide mutants. J Bacteriol. 1975 Nov;124(2):942–958. doi: 10.1128/jb.124.2.942-958.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Then R. L. Ability of newer beta-lactam antibiotics to induce beta-lactamase production in Enterobacter cloacae. Eur J Clin Microbiol. 1987 Aug;6(4):451–455. doi: 10.1007/BF02013109. [DOI] [PubMed] [Google Scholar]
  25. Then R. L., Angehrn P. Trapping of nonhydrolyzable cephalosporins by cephalosporinases in Enterobacter cloacae and Pseudomonas aeruginosa as a possible resistance mechanism. Antimicrob Agents Chemother. 1982 May;21(5):711–717. doi: 10.1128/aac.21.5.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Then R. L., Angehrn P. Ways to overcome cephalosporinase-mediated beta-lactam resistance in Enterobacter cloacae. Chemioterapia. 1985 Feb;4(1):83–89. [PubMed] [Google Scholar]
  27. Then R. L., Charnas R. L., Kocher H. P., Manneberg M., Röthlisberger U., Stocker J. Biochemical characterization of type A and type B beta-lactamase from Enterobacter cloacae. Rev Infect Dis. 1988 Jul-Aug;10(4):714–720. doi: 10.1093/clinids/10.4.714. [DOI] [PubMed] [Google Scholar]
  28. Vu H., Nikaido H. Role of beta-lactam hydrolysis in the mechanism of resistance of a beta-lactamase-constitutive Enterobacter cloacae strain to expanded-spectrum beta-lactams. Antimicrob Agents Chemother. 1985 Mar;27(3):393–398. doi: 10.1128/aac.27.3.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Waley S. G. An explicit model for bacterial resistance: application to beta-lactam antibiotics. Microbiol Sci. 1987 May;4(5):143–146. [PubMed] [Google Scholar]
  30. Werner V., Sanders C. C., Sanders W. E., Jr, Goering R. V. Role of beta-lactamases and outer membrane proteins in multiple beta-lactam resistance of Enterobacter cloacae. Antimicrob Agents Chemother. 1985 Apr;27(4):455–459. doi: 10.1128/aac.27.4.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zimmermann W., Rosselet A. Function of the outer membrane of Escherichia coli as a permeability barrier to beta-lactam antibiotics. Antimicrob Agents Chemother. 1977 Sep;12(3):368–372. doi: 10.1128/aac.12.3.368. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES