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. 1980 Oct;18(4):629–637. doi: 10.1128/aac.18.4.629

In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae.

R Williamson, R Hakenbeck, A Tomasz
PMCID: PMC284061  PMID: 7447421

Abstract

The interactions of several beta-lactam antibiotics with the penicillin-binding proteins (PBPs) of Streptococcus pneumoniae have been studied using whole organisms treated with such antibiotics and subsequently with [3H]benzylpenicillin. Differences in chemical structure were shown to cause major and selective changes in the affinities of the beta-lactams for the PBPs Only 4 of the 28 compounds tested induced a specific morphological effect (enlargement of the equatorial region) under the particular conditions tested. In 12 of the 18 beta-lactams studied, a close correlation was found between the minimal inhibitory concentrations and the concentrations required to half-saturate PBP2b. However, such a correlation was no longer apparent when the bacteria were treated with the antibiotics at their minimal inhibitory concentrations. These findings are discussed in the context of various approaches that have been used to identify the growth-inhibitory targets of beta-lactam antibiotics in bacteria.

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Selected References

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

  1. 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]
  2. Curtis N. A., Orr D., Ross G. W., Boulton M. G. Affinities of penicillins and cephalosporins for the penicillin-binding proteins of Escherichia coli K-12 and their antibacterial activity. Antimicrob Agents Chemother. 1979 Nov;16(5):533–539. doi: 10.1128/aac.16.5.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Hakenbeck R., Tarpay M., Tomasz A. Multiple changes of penicillin-binding proteins in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Mar;17(3):364–371. doi: 10.1128/aac.17.3.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Iida K., Hirata S., Nakamuta S., Koike M. Inhibition of cell division of Escherichia coli by a new synthetic penicillin, piperacillin. Antimicrob Agents Chemother. 1978 Aug;14(2):257–266. doi: 10.1128/aac.14.2.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Iwaya M., Strominger J. L. Simultaneous deletion of D-alanine carboxypeptidase IB-C and penicillin-binding component IV in a mutant of Escherichia coli K12. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2980–2984. doi: 10.1073/pnas.74.7.2980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kitano K., Tomasz A. Triggering of autolytic cell wall degradation in Escherichia coli by beta-lactam antibiotics. Antimicrob Agents Chemother. 1979 Dec;16(6):838–848. doi: 10.1128/aac.16.6.838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. LACKS S., HOTCHKISS R. D. A study of the genetic material determining an enzyme in Pneumococcus. Biochim Biophys Acta. 1960 Apr 22;39:508–518. doi: 10.1016/0006-3002(60)90205-5. [DOI] [PubMed] [Google Scholar]
  9. Matsuhashi M., Maruyama I. N., Takagaki Y., Tamaki S., Nishimura Y., Hirota Y. Isolation of a mutant of Escherichia coli lacking penicillin-sensitive D-alanine carboxypeptidase IA. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2631–2635. doi: 10.1073/pnas.75.6.2631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Matsuhashi M., Takagaki Y., Maruyama I. N., Tamaki S., Nishimura Y., Suzuki H., Ogino U., Hirota Y. Mutants of Escherichia coli lacking in highly penicillin-sensitive D-alanine carboxypeptidase activity. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2976–2979. doi: 10.1073/pnas.74.7.2976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moore B. A., Jevons S., Brammer K. W. Peptidoglycan transpeptidase inhibition in Pseudomonas aeruginosa and Escherichia coli by Penicillins and Cephalosporins. Antimicrob Agents Chemother. 1979 Apr;15(4):513–517. doi: 10.1128/aac.15.4.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Nozaki Y., Imada A., Yoneda M. SCE-963, a new potent cephalosporin with high affinity for penicillin-binding proteins 1 and 3 of Escherichia coli. Antimicrob Agents Chemother. 1979 Jan;15(1):20–27. doi: 10.1128/aac.15.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ohya S., Yamazaki M., Sugawara S., Matsuhashi M. Penicillin-binding proteins in Proteus species. J Bacteriol. 1979 Jan;137(1):474–479. doi: 10.1128/jb.137.1.474-479.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ohya S., Yamazaki M., Sugawara S., Tamaki S., Matsuhashi M. New cephamycin antibiotic, CS-1170: binding affinity to penicillin-binding proteins and inhibition of peptidoglycan cross-linking reactions in Escherichia coli. Antimicrob Agents Chemother. 1978 Nov;14(5):780–785. doi: 10.1128/aac.14.5.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oka T., Fujita H. Effect of beta-lactam antibiotics on in vitro peptidoglycan cross-linking by a particulate fraction from Escherichia coli K-12 and Bacillus megaterium KM. Antimicrob Agents Chemother. 1978 Oct;14(4):625–627. doi: 10.1128/aac.14.4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Reynolds P. E., Shepherd S. T., Chase H. A. Identification of the binding protein which may be the target of penicillin action in Bacillus megaterium. Nature. 1978 Feb 9;271(5645):568–570. doi: 10.1038/271568a0. [DOI] [PubMed] [Google Scholar]
  18. Rodriguez W. J., Saz A. K. Differential binding of penicillin by membrane fractions from penicillin-susceptible and -resistant gonococci. Antimicrob Agents Chemother. 1978 Apr;13(4):589–597. doi: 10.1128/aac.13.4.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Shepherd S. T., Chase H. A., Reynolds P. E. The separation and properties of two penicillin-binding proteins from Salmonella typhimurium. Eur J Biochem. 1977 Sep;78(2):521–523. doi: 10.1111/j.1432-1033.1977.tb11765.x. [DOI] [PubMed] [Google Scholar]
  20. Spratt B. G. Distinct penicillin binding proteins involved in the division, elongation, and shape of Escherichia coli K12. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2999–3003. doi: 10.1073/pnas.72.8.2999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Spratt B. G., Pardee A. B. Penicillin-binding proteins and cell shape in E. coli. Nature. 1975 Apr 10;254(5500):516–517. doi: 10.1038/254516a0. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Suzuki H., Nishimura Y., Hirota Y. On the process of cellular division in Escherichia coli: a series of mutants of E. coli altered in the penicillin-binding proteins. Proc Natl Acad Sci U S A. 1978 Feb;75(2):664–668. doi: 10.1073/pnas.75.2.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tamaki S., Nakajima S., Matsuhashi M. Thermosensitive mutation in Escherichia coli simultaneously causing defects in penicillin-binding protein-1Bs and in enzyme activity for peptidoglycan synthesis in vitro. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5472–5476. doi: 10.1073/pnas.74.12.5472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tomasz A., Waks S. Mechanism of action of penicillin: triggering of the pneumococcal autolytic enzyme by inhibitors of cell wall synthesis. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4162–4166. doi: 10.1073/pnas.72.10.4162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zighelboim S., Tomasz A. Penicillin-binding proteins of multiply antibiotic-resistant South African strains of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Mar;17(3):434–442. doi: 10.1128/aac.17.3.434. [DOI] [PMC free article] [PubMed] [Google Scholar]

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