1887

Abstract

In a clinical isolate of different states of low and high resistance to different β-lactam antibiotics considered to be -lactamase-stable, viz. cefotaxime, ceftizoxime, ceftazidime, aztreonam, cefoxitin and imipenem, were found to be connected with the presence of constitutively overproduced, chromosomally encoded -lactamase at concentrations in the bacterial periplasm of 0·4 and 0·9 m, respectively. All the antibiotics were degraded by the -lactamase. However, kinetic constants varied widely: from 92 to 0·012 µ, and from 3·4 to 2 × 10 s. The relative contributions to resistance by the functioning of periplasmic -lactamase, resynthesis of this enzyme, and limitation of antibiotic penetration by the bacterial outer membrane were analysed by computer simulations according to steady-state and non-steady-state models of interactions in the periplasm. Results for cefotaxime, ceftizoxime, ceftazidime, aztreonam and latamoxef revealed overproduced -lactamase as the sole cause of the state of low resistance while antibiotic permeability was the same as in non-resistant strains. In contrast, high resistance was due to -lactamase action and decreased permeability of antibiotics. For resistance to aztreonam, only, immobilization of the antibiotic as covalent acyl-enzyme by newly synthesized -lactamase was essential. For cefoxitin, ampicillin and imipenem the analyses indicated that additional resistance factors may play a role, e.g. induction of -lactamase.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-135-5-1275
1989-05-01
2022-01-23
Loading full text...

Full text loading...

/deliver/fulltext/micro/135/5/mic-135-5-1275.html?itemId=/content/journal/micro/10.1099/00221287-135-5-1275&mimeType=html&fmt=ahah

References

  1. Atkinson B.A. 1981; Species incidence, trends of susceptibility to antibiotics in the U.S. and minimum inhibitory concentrations. In Antibiotics in Laboratory Medicine pp. 607–722 Lorian V. Edited by Baltimore and London: Williams & Wilkins;
    [Google Scholar]
  2. Beckwith D.G., Jahre J.A. 1980; Role of a cefoxitin-inducible beta-lactamase in a case of breakthrough bacteremia. Journal of Clinical Microbiology 12:517–520
    [Google Scholar]
  3. Brass J.M. 1986; The cell envelope of Gramnegative bacteria: new aspects of its function in transport and chemotaxis. Current Topics in Microbiology and Immunology 129:1–29
    [Google Scholar]
  4. Büscher K.H., Cullmann W., Dick W., Opferkuch W. 1987; Imipenem resistance in Pseudomonas aeruginosa resulting from diminished expression of an outer membrane protein. Antimicrobial Agents and Chemotherapy 31:703–708
    [Google Scholar]
  5. Bush K., Freudenberger J.S., Sykes R. 1982; Interaction of azthreonam and related monobactams with β-lactamases from Gram-negative bacteria. Antimicrobial Agents and Chemotherapy 22:414–420
    [Google Scholar]
  6. Bush K., Tanaka S.K., Bonner D.P., Sykes R. B. 1985; Resistance caused by decreased penetration of β-actam antibiotics into Enterobacter cloacae . Antimicrobial Agents and Chemotherapy 27:555–560
    [Google Scholar]
  7. Cltrl N., Zyk N. 1965; The interaction of penicillinase with penicillins. IV. Structural aspects of catalytic and non-catalytic interactions. Bio-chimica et biophysica acta 99:427–441
    [Google Scholar]
  8. Cullmann W., Opferkuch W., Stieglitz M., Werkmeister U. 1982; A comparison of the antibacterial activities of N-formimidoyl-thiena-mycin (MK 0787) with those of other recently developed β-lactam derivatives. Antimicrobial Agents and Chemotherapy 22:302–307
    [Google Scholar]
  9. Curtis N.A.C., Eisenstadt R.L., Rudd C., Whites A.J. 1986; Inducible type I β-lactamases of Gram-negative bacteria and resistance to β-lactam antibiotics. Journal of Antimicrobial Chemotherapy 17:51–61
    [Google Scholar]
  10. De meester F., Joris B., Reckinger G., Belle-Froid-Bourguignon C., Frère J.M., Waley S.G. 1987; Automated analysis of enzyme inactivation phenomena. Application to β-lactamases and DD-peptidases. Biochemical Pharmacology 36:2393–2403
    [Google Scholar]
  11. Eisenthal R., Cornish-Bowden A. 1974; The direct linear plot-a new graphical procedure for the estimation of enzyme kinetic parameters. Biochemical Journal 139:715–720
    [Google Scholar]
  12. Frère J.M. 1989; Quantitative relationship between sensitivity to β-lactam antibiotics and β-lactamase production in Gram-negative bacteria. I. Steady state treatment. Biochemical Pharmacology 38:1415–1426
    [Google Scholar]
  13. Frère J.M., Joris B. 1988; β-Lactamase induced resistance. In Antibiotic Inhibition of Bacterial Cell surface Assembly and Function pp. 468–480 Actor P., Daneo-Moore L., Higgins M., Salton M.R.J., Shockman G.D. Edited by Washington, DC: American Society for Microbiology;
    [Google Scholar]
  14. Frère J.M., Dormans C., Lenzini V.M., Duyckaerts C. 1982; Interaction of clavulanate with β-lactamases in Streptomyces albus G and Actinomadura R 39. Biochemical Journal 207:429–436
    [Google Scholar]
  15. Frère J.M., Joris B., Crine M., Martin H.H. 1989; Quantitative relationship between sensitivity to β-lactam antibiotics and β-lactamase production in Gram-negative bacteria. II. Non-steady state treatment and progress curves. Biochemical Pharmacology 38:1427–1434
    [Google Scholar]
  16. Galleni M., Frère J.M. 1988; A survey of the kinetic parameters of class C β-lactamases. I. Penicillins. Biochemical Journal 255:119–122
    [Google Scholar]
  17. Galleni M., Amicosante G., Frère J.M. 1988; A survey of the kinetic parameters of class C β-lactamases. II. Cephalosporins and other β-lactam compounds. Biochemical Journal 255:123–129
    [Google Scholar]
  18. Gootz T.D., Sanders C.C., Goering R.V. 1982; Resistance to cefamandole: derepression of beta-lactamase by cefoxitin and mutation in Enterobacter cloacae . Journal of Infectious Diseases 146:34–42
    [Google Scholar]
  19. Gootz T.D., Jackson D.B., Sherris J.C. 1984; Development of resistance to cephalosporins in clinical strains of Citrobacter spp. Antimicrobial Agents and Chemotherapy 25:591–595
    [Google Scholar]
  20. Hazelbauer G.L. 1979; The outer membrane and chemotaxis: indirect influences and secondary involvements. In Bacterial Outer Membranes pp. 449–473 Inouye M. Edited by New York: John Wiley;
    [Google Scholar]
  21. Hobot J.A., Carlemalm E., Villiger W. 1984; Periplasmic gel: new concept resulting from the reinvestigation of bacterial cell envelope ultrastructure by new methods. Journal of Bacteriology 160:143–152
    [Google Scholar]
  22. Joris B., De Meester F., Galleni M., Masson S., Dusart J., Frère J.M., Van Beeumen J., Bush K., Sykes R. 1986; Properties of a class C β-lactamase from Serratia marcescens . Biochemical Journal 239:581–586
    [Google Scholar]
  23. Kelly J.A., Frère J.M., Duez C., Ghuysen J.M. 1981; Interactions between non-classical β-lactam compounds and the β-lactamases of Actinomadura R39 and Streptomyces albus G. Biochemical Journal 199:137–143
    [Google Scholar]
  24. Laemmli U.K., Favre M. 1973; Maturation of the head of bacteriophage T4. Journal of Molecular Biology 80:575–599
    [Google Scholar]
  25. Lampe M.G., Allan B.J., Minshew B.H., Sherris J.C. 1982; Mutational enzymatic resistance of Enterobacter species to beta-lactam antibiotics. Antimicrobial Agents and Chemotherapy 21:655–660
    [Google Scholar]
  26. Lindberg F., Normark S. 1986; Contribution of chromosomal β-lactamase to β-lactam resistance in Enterobacteria. Reviews of Infectious Diseases 8: (suppl.3) 292–304
    [Google Scholar]
  27. Livermore D.M., Riddle S.J., Davy K.W.M. 1986; Hydrolytic model of cefotaxime and ceftriaxone resistance in β-lactamase-derepressed Enterobacter cloacae . Journal of Infectious Diseases 153:619–622
    [Google Scholar]
  28. Marchou B., Bellido F., Charnas R., Lucain C., Pechère J.C. 1987; Contribution of β-lactam hydrolysis and outer membrane permeability to ceftriaxone resistance in Enterobacter cloacae . Antimicrobial Agents and Chemotherapy 31:1589–1595
    [Google Scholar]
  29. Marquet A., Dusart J., Ghuysen J.M., Perkins H.R. 1974; Membrane-bound transpeptidase and penicillin-binding sites in Streptomyces strain R 61. European Journal of Biochemistry 46:515–523
    [Google Scholar]
  30. Martin H.H., Schmidt B., Bräutigam S., Noguchi H., Matshuhashi M. 1988; Initiation of induction of chromosomal β-lactamase in Gramnegative bacteria by binding of inducing β-lactam antibiotics to low-molecular-weight penicillin-binding proteins. In Antibiotic Inhibition of Bacterial Cell surface Assembly and Function pp. 494–501 Actor P., Daneo-Moore L., Higgins M., Salton M. R.J., Shockman G.D. Edited by Washington, DC: American Society for Microbiology;
    [Google Scholar]
  31. Matthew M. 1979; Plasmid mediated β-lactamase of Gram-negative bacteria: properties and distribution. Journal of Antimicrobial Chemotherapy 5:349–358
    [Google Scholar]
  32. Matthew M., Harris A., Marshall M., Ross G.W. 1975; The use of analytical isoelectric focusing for detection and identification of β-lactamases. Journal of General Microbiology 88:169–178
    [Google Scholar]
  33. Minami S., Yotsuji A., Inoue M., Mitsuhashi S. 1980; Induction of β-lactamase by various β-lactam antibiotics in Enterobacter cloacae . Antimicrobial Agents and Chemotherapy 18:382–385
    [Google Scholar]
  34. Nikaido H. 1979; Nonspecific transport through the outer membrane. In Bacterial Outer Membranes pp. 361–407 Inouye M. Edited by New York: John Wiley;
    [Google Scholar]
  35. Nikaido H., Normark S. 1987; Sensitivity of Escherichia coli to various β-lactams is determined by the interplay of outer membrane permeability and degradation by periplasmic β-lactamases: a quantitative predictive treatment. Molecular Microbiology 1:29–36
    [Google Scholar]
  36. Sanders C.C., Sanders W.E. 1979; Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases. Antimicrobial Agents and Chemotherapy 15:792–797
    [Google Scholar]
  37. Sawai T., Kanno M., Tsukamoto K. 1982; Characterization of eight β-lactamases from Gramnegative bacteria. Journal of Bacteriology 152:567–571
    [Google Scholar]
  38. Seeberg A.H., Tolxdorff-Neutzling R.M., Wiedemann B. 1983; Chromosomal β-lactamases of Enterobacter cloacae are responsible for resistance to third-generation cephalosporins. Antimicrobial Agents and Chemotherapy 23:918–925
    [Google Scholar]
  39. Tajima M., Masuyoshi S., Inoue M., Takenouchi Y., Sugawara S., Mitsuhashi S. 1981; Purification and properties of β-lactamases from Serratia marcescens . Journal of General Microbiology 126:179–184
    [Google Scholar]
  40. Vu H., Nikaido H. 1985; Role of β-lactam hydrolysis in the mechanism of resistance of a β-lactamase-constitutive Enterobacter cloacae strain to expanded-spectrum β-lactams. Antimicrobial Agents and Chemotherapy 27:393–398
    [Google Scholar]
  41. Waley S.G. 1987; An explicit model for bacterial resistance: application to β-lactam antibiotics. Microbiological Sciences 4:143–146
    [Google Scholar]
  42. Zimmermann W., Rosselet A. 1977; Function of the outer membrane of Escherichia coli as a permeability barrier to beta-lactam antibiotics. Antimicrobial Agents and Chemotherapy 12:368–372
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-135-5-1275
Loading
/content/journal/micro/10.1099/00221287-135-5-1275
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error