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. 1982 Mar;21(3):492–497. doi: 10.1128/aac.21.3.492

Penem derivatives: beta-lactamase stability and affinity for penicillin-binding proteins in Escherichia coli.

S Ohya, Y Utsui, S Sugawara, M Yamazaki
PMCID: PMC181920  PMID: 7049076

Abstract

Penem derivatives, a new group of beta-lactam antibiotics with potent activities against a wide range of bacteria, including Pseudomonas aeruginosa, were tested for their stability against hydrolysis by beta-lactamases purified from clinical isolates of Morganella morganii. Proteus vulgaris, and Escherichia coli and by a penicillinase from Bacillus cereus. Penems having 6 alpha substituents, such as hydroxyethyl, hydroxymethyl, and ethyl groups, were very stable against hydrolysis by each of the enzymes. Penems having no 6 alpha substituents were easily hydrolyzed by P. vulgaris and E. coli enzymes, whereas they were rather stable against hydrolysis by M. morganii and B. cereus enzymes, a typical cephalosporinase and penicillinase, respectively. Affinity of the penems for E. coli penicillin-binding proteins (PBPs) was also tested. beta-Lactamase-stable penems having a 6 alpha-hydroxyethyl group showed high affinity for PBP-4, -5, and -6 as well as for PBP-1A, -1Bs, and -2. However, the penems having no 6 alpha substituents showed a far lower affinity for PBP-4, -5, and -6 than that shown by the corresponding 6 alpha-hydroxyethyl penems. Among the penems tested, affinity for PBP-4, -5, and -6 was closely related to their beta-lactamase stability, as was the case among cephamycins and cephalosporins. Effects of the penems on the morphology of a strain of E. coli are also described.

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Selected References

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

  1. Daoust D. R., Onishi H. R., Wallick H., Hendlin D., Stapley E. O. Cephamycins, a new family of beta-lactam antibiotics: antibacterial activity and resistance to beta-lactamase degradation. Antimicrob Agents Chemother. 1973 Feb;3(2):254–261. doi: 10.1128/aac.3.2.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Frere J., Ghuysen J., Vanderhaeghe H., Adriaens P., Degelaen J., De Graeve J. Fate of thiazolidine ring during fragmentation of penicillin by exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61. Nature. 1976 Apr 1;260(5550):451–454. doi: 10.1038/260451a0. [DOI] [PubMed] [Google Scholar]
  3. Fu K. P., Neu H. C. beta-lactamase stability of HR 756, a novel cephalosporin, compared to that of cefuroxime and cefoxitin. Antimicrob Agents Chemother. 1978 Sep;14(3):322–326. doi: 10.1128/aac.14.3.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fujii-Kuriyama Y., Yamamoto M., Sugawara S. Purification and properties of beta-lactamase from Proteus morganii. J Bacteriol. 1977 Sep;131(3):726–734. doi: 10.1128/jb.131.3.726-734.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hammarström S., Strominger J. L. Degradation of penicillin G to phenylacetylglycine by D-alanine carboxypeptidase from Bacillus stearothermophilus. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3463–3467. doi: 10.1073/pnas.72.9.3463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Neu H. C., Fu K. P. Cefuroxime, a beta-lactamase-resistant cephalosporin with a broad spectrum of gram-positive and -negative activity. Antimicrob Agents Chemother. 1978 Apr;13(4):657–664. doi: 10.1128/aac.13.4.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Nishino T., Nakazawa S. Morphological changes in Staphylococcus aureus and Escherichia coli exposed to cephalexin. Jpn J Microbiol. 1972 Mar;16(2):83–94. doi: 10.1111/j.1348-0421.1972.tb00633.x. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Oida S., Yoshida A., Hayashi T., Takeda N., Nishimura T., Ohki E. Synthesis of penems and their antibacterial activities. J Antibiot (Tokyo) 1980 Jan;33(1):107–109. doi: 10.7164/antibiotics.33.107. [DOI] [PubMed] [Google Scholar]
  12. Sakamoto M., Iguchi H., Okamura K., Hori S., Fukagawa Y., Ishikura T., Lein J. PS-5, a new beta-lactam antibiotic. II. Antimicrobial activity. J Antibiot (Tokyo) 1979 Apr;32(4):272–279. doi: 10.7164/antibiotics.32.272. [DOI] [PubMed] [Google Scholar]
  13. Spratt B. G., Jobanputra V., Zimmermann W. Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escherichia coli K-12. Antimicrob Agents Chemother. 1977 Sep;12(3):406–409. doi: 10.1128/aac.12.3.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Tally F. P., Jacobus N. V., Gorbach S. L. In vitro activity of thienamycin. Antimicrob Agents Chemother. 1978 Sep;14(3):436–438. doi: 10.1128/aac.14.3.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Tamura T., Imae Y., Strominger J. L. Purification to homogeneity and properties of two D-alanine carboxypeptidases I From Escherichia coli. J Biol Chem. 1976 Jan 25;251(2):414–423. [PubMed] [Google Scholar]
  16. Weaver S. S., Bodey G. P., LeBlanc B. M. Thienamycin: new beta-lactam antibiotic with potent broad-spectrum activity. Antimicrob Agents Chemother. 1979 Apr;15(4):518–521. doi: 10.1128/aac.15.4.518. [DOI] [PMC free article] [PubMed] [Google Scholar]

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