Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1984 May;25(5):607–611. doi: 10.1128/aac.25.5.607

Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A.

P Angehrn, M J Hall, W J Lloyd, D Westmacott
PMCID: PMC185597  PMID: 6428312

Abstract

The phosphonopeptide L- norvalyl -L-1- aminoethylphosphonic acid [ Nva -Ala(P)] has been studied in combination with 12 beta-lactam antibiotics for activity against Pseudomonas aeruginosa. Nocardicin A was found to give the most potent synergistic combination with Nva -Ala(P). This interaction was widely observed in clinical isolates of P. aeruginosa in vitro and in a mouse septicemia model. Synergy was also observed in vitro and in vivo in several other species, including Proteus mirabilis, indole-positive Proteus spp., and Serratia marcescens. The interaction between Nva -Ala(P) and nocardicin A involved a strongly bacteriolytic mechanism. In addition, the individual components were complementary to one another in their action against organisms not showing synergy. These properties resulted in a broad spectrum of activity of the combination Nva -Ala(P) plus nocardicin A when used to treat experimental gram-negative bacterial infections.

Full text

PDF
607

Selected References

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

  1. Allen J. G., Atherton F. R., Hall M. J., Hassall C. H., Holmes S. W., Lambert R. W., Nisbet L. J., Ringrose P. S. Phosphonopeptides as antibacterial agents: alaphosphin and related phosphonopeptides. Antimicrob Agents Chemother. 1979 May;15(5):684–695. doi: 10.1128/aac.15.5.684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atherton F. R., Hall M. J., Hassall C. H., Holmes S. W., Lambert R. W., Lloyd W. J., Nisbet L. J., Ringrose P. S., Westmacott D. Antibacterial properties of alafosfalin combined with cephalexin. Antimicrob Agents Chemother. 1981 Oct;20(4):470–476. doi: 10.1128/aac.20.4.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Atherton F. R., Hall M. J., Hassall C. H., Holmes S. W., Lambert R. W., Lloyd W. J., Ringrose P. S. Phosphonopeptide antibacterial agents related to alafosfalin: design, synthesis, and structure-activity relationships. Antimicrob Agents Chemother. 1980 Dec;18(6):897–905. doi: 10.1128/aac.18.6.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Atherton F. R., Hall M. J., Hassall C. H., Lambert R. W., Lloyd W. J., Ringrose P. S. Phosphonopeptides as antibacterial agents: mechanism of action of alaphosphin. Antimicrob Agents Chemother. 1979 May;15(5):696–705. doi: 10.1128/aac.15.5.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Atherton F. R., Hall M. J., Hassall C. H., Lambert R. W., Lloyd W. J., Ringrose P. S., Westmacott D. Antibacterial activity and mechanism of action of phosphonopeptides based on aminomethylphosphonic acid. Antimicrob Agents Chemother. 1982 Oct;22(4):571–578. doi: 10.1128/aac.22.4.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Atherton F. R., Hall M. J., Hassall C. H., Lambert R. W., Ringrose P. S. Phosphonopeptides as antibacterial agents: rationale, chemistry, and structure-activity relationships. Antimicrob Agents Chemother. 1979 May;15(5):677–683. doi: 10.1128/aac.15.5.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Banks R. M., O'Grady F. Therapeutic significance of nocardicin A stimulation of phagocyte function in experimental Pseudomonas aeruginosa infection. Br J Exp Pathol. 1983 Apr;64(2):231–237. [PMC free article] [PubMed] [Google Scholar]
  8. Berenbaum M. C. A method for testing for synergy with any number of agents. J Infect Dis. 1978 Feb;137(2):122–130. doi: 10.1093/infdis/137.2.122. [DOI] [PubMed] [Google Scholar]
  9. Berenguer J., De Pedro M. A., Vázquez D. V. Interaction of nocardicin A with the penicillin-binding proteins of Escherichia coli in intact cells and in purified cell envelopes. Eur J Biochem. 1982 Aug;126(1):155–159. doi: 10.1111/j.1432-1033.1982.tb06760.x. [DOI] [PubMed] [Google Scholar]
  10. Berenguer J., de Pedro M. A., Vázquez D. Induction of cell lysis in Escherichia coli: cooperative effect of nocardicin A and mecillinam. Antimicrob Agents Chemother. 1982 Feb;21(2):195–200. doi: 10.1128/aac.21.2.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Curtis N. A., Orr D., Boulton M. G., Ross G. W. Penicillin-binding proteins of Pseudomonas aeruginosa. Comparison of two strains differing in their resistance to beta-lactam antibiotics. J Antimicrob Chemother. 1981 Feb;7(2):127–136. doi: 10.1093/jac/7.2.127. [DOI] [PubMed] [Google Scholar]
  12. ELION G. B., SINGER S., HITCHINGS G. H. Antagonists of nucleic acid derivatives. VIII. Synergism in combinations of biochemically related antimetabolites. J Biol Chem. 1954 Jun;208(2):477–488. [PubMed] [Google Scholar]
  13. Hall M. J., Middleton R. F., Westmacott D. The fractional inhibitory concentration (FIC) index as a measure of synergy. J Antimicrob Chemother. 1983 May;11(5):427–433. doi: 10.1093/jac/11.5.427. [DOI] [PubMed] [Google Scholar]
  14. Mine Y., Nonoyama S., Kojo H., Fukada S., Nishida M. Nocardicin A, a new monocyclic beta-lactam antibiotic V. In vivo evaluation. J Antibiot (Tokyo) 1977 Nov;30(11):932–937. doi: 10.7164/antibiotics.30.932. [DOI] [PubMed] [Google Scholar]
  15. Nishida M., Mine Y., Nonoyama S., Kojo H. Nocardicin A, a new monocyclic beta-lactam antibiotic III. In vitro evaluation. J Antibiot (Tokyo) 1977 Nov;30(11):917–925. doi: 10.7164/antibiotics.30.917. [DOI] [PubMed] [Google Scholar]
  16. Noguchi H., Matsuhashi M., Mitsuhashi S. Comparative studies of penicillin-binding proteins in Pseudomonas aeruginosa and Escherichia coli. Eur J Biochem. 1979 Oct;100(1):41–49. doi: 10.1111/j.1432-1033.1979.tb02031.x. [DOI] [PubMed] [Google Scholar]
  17. Noguchi H., Matsuhashi M., Takaoka M., Mitsuhashi S. New antipseudomonal penicillin, PC-904: affinity to penicillin-binding proteins and inhibition of the enzyme cross-linking peptidoglycan. Antimicrob Agents Chemother. 1978 Oct;14(4):617–624. doi: 10.1128/aac.14.4.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zimmermann W. Penetration of beta-lactam antibiotics into their target enzymes in Pseudomonas aeruginosa: comparison of a highly sensitive mutant with its parent strain. Antimicrob Agents Chemother. 1980 Jul;18(1):94–100. doi: 10.1128/aac.18.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES