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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1975 Jul;72(7):2621–2625. doi: 10.1073/pnas.72.7.2621

Sulfonamide resistance mechanism in Escherichia coli: R plasmids can determine sulfonamide-resistant dihydropteroate synthases.

E M Wise Jr, M M Abou-Donia
PMCID: PMC432821  PMID: 1101260

Abstract

Several natural isolate E. coli strains highly resistant to sulfonamides and antibiotics are shown to contain a sulfonamide-resistant dihydropteroate synthase (2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine-diphosphate:4-aminobenzoate 2-amino-4-hydroxydihydropteridine-6-methenyltransferase, EC 2.5.1.15) in addition to the normal sensitive enzyme. The resistant dihydropteroate synthases examined are determined by an R plasmid and are smaller and less heat stable than the normal sulfonamide-sensitive enzyme. One synthase resistant to any sulfonamide tested, and to sulfanilic and arsanilic acids, was still inhibited by several non-sulfonamide analogs of p-aminobenzoate. Citrobacter and Klebsiella pneumoniae strains also show similar mechanisms of sulfonamide resistance.

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Selected References

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

  1. Amyes S. G., Smith J. T. R-factor trimethoprim resistance mechanism: an insusceptible target site. Biochem Biophys Res Commun. 1974 May 20;58(2):412–418. doi: 10.1016/0006-291x(74)90380-5. [DOI] [PubMed] [Google Scholar]
  2. Andrews P. The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochem J. 1965 Sep;96(3):595–606. doi: 10.1042/bj0960595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bauer A. W., Kirby W. M., Sherris J. C., Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966 Apr;45(4):493–496. [PubMed] [Google Scholar]
  4. Benveniste R., Davies J. Mechanisms of antibiotic resistance in bacteria. Annu Rev Biochem. 1973;42:471–506. doi: 10.1146/annurev.bi.42.070173.002351. [DOI] [PubMed] [Google Scholar]
  5. Burchall J. J., Hitchings G. H. Inhibitor binding analysis of dihydrofolate reductases from various species. Mol Pharmacol. 1965 Sep;1(2):126–136. [PubMed] [Google Scholar]
  6. Bushby S. R. Combined antibacterial action in vitro of trimethoprim and sulphonamides. The in vitro nature of synergy. Postgrad Med J. 1969 Nov;45(Suppl):10–18. [PubMed] [Google Scholar]
  7. Clowes R. C. Molecular structure of bacterial plasmids. Bacteriol Rev. 1972 Sep;36(3):361–405. doi: 10.1128/br.36.3.361-405.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Datta N., Hedges R. W. Host ranges of R factors. J Gen Microbiol. 1972 May;70(3):453–460. doi: 10.1099/00221287-70-3-453. [DOI] [PubMed] [Google Scholar]
  9. Datta N., Hedges R. W., Shaw E. J., Sykes R. B., Richmond M. H. Properties of an R factor from Pseudomonas aeruginosa. J Bacteriol. 1971 Dec;108(3):1244–1249. doi: 10.1128/jb.108.3.1244-1249.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davies J. E., Rownd R. Transmissible multiple drug resistance in Enterobacteriaceae. Science. 1972 May 19;176(4036):758–768. doi: 10.1126/science.176.4036.758. [DOI] [PubMed] [Google Scholar]
  11. Davis B. D., Maas W. K. Analysis of the Biochemical Mechanism of Drug Resistance in Certain Bacterial Mutants. Proc Natl Acad Sci U S A. 1952 Sep;38(9):775–785. doi: 10.1073/pnas.38.9.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grunberg E., DeLorenzo W. F. Potentiation of sulfonamides and antibiotics by trimethoprim [2,4-diamino-5-(3,4,5-trimethoxybenzyl) pyrimidine]. Antimicrob Agents Chemother (Bethesda) 1966;6:430–433. [PubMed] [Google Scholar]
  13. Helinski D. R. Plasmid determined resistance to antibiotics: molecular properties of R factors. Annu Rev Microbiol. 1973;27:437–470. doi: 10.1146/annurev.mi.27.100173.002253. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Ortiz P. J., Hotchkiss R. D. The enzymatic synthesis of dihydrofolate and dihydropteroate in cell-free preparations from wild-type and sulfonamide-resistant pneumococcus. Biochemistry. 1966 Jan;5(1):67–74. doi: 10.1021/bi00865a010. [DOI] [PubMed] [Google Scholar]
  16. ROTH B., FALCO E. A., HITCHINGS G. H., BUSHBY S. R. 5-BENZYL-2,4-DIAMINOPYRIMIDINES AS ANTIBACTERIAL AGENTS. I. SYNTHESIS AND ANTIBACTERIAL ACTIVITY IN VITRO. J Med Pharm Chem. 1962 Nov;91:1103–1123. doi: 10.1021/jm01241a004. [DOI] [PubMed] [Google Scholar]
  17. Reisberg B., Herzog J., Weinstein L. In vitro antibacterial activity of trimethoprim alone and combined with sulfonamides. Antimicrob Agents Chemother (Bethesda) 1966;6:424–429. [PubMed] [Google Scholar]
  18. Richey D. P., Brown G. M. The biosynthesis of folic acid. IX. Purification and properties of the enzymes required for the formation of dihydropteroic acid. J Biol Chem. 1969 Mar 25;244(6):1582–1592. [PubMed] [Google Scholar]
  19. SHIOTA T., DISRAELY M. N., MCCANN M. P. THE ENZYMATIC SYNTHESIS OF FOLATE-LIKE COMPOUNDS FROM HYDROXYMETHYLDIHYDROPTERIDINE PYROPHOSPHATE. J Biol Chem. 1964 Jul;239:2259–2266. [PubMed] [Google Scholar]
  20. Shaw W. V. Biochemical mechanisms of transferable drug resistance. Adv Pharmacol Chemother. 1971;9:131–172. doi: 10.1016/s1054-3589(08)60446-9. [DOI] [PubMed] [Google Scholar]
  21. Shiota T., Baugh C. M., Jackson R., Dillard R. The enzymatic synthesis of hydroxymethyldihydropteridine pyrophosphate and dihydrofolate. Biochemistry. 1969 Dec;8(12):5022–5028. doi: 10.1021/bi00840a052. [DOI] [PubMed] [Google Scholar]
  22. Sköld O., Widh A. A new dihydrofolate reductase with low trimethoprim sensitivity induced by an R factor mediating high resistance to trimethoprim. J Biol Chem. 1974 Jul 10;249(13):4324–4325. [PubMed] [Google Scholar]
  23. Tillett W. S., Cambier M. J., Harris W. H. SULFONAMIDE-FAST PNEUMOCOCCI. A CLINICAL REPORT OF TWO CASES OF PNEUMONIA TOGETHER WITH EXPERIMENTAL STUDIES ON THE EFFECTIVENESS OF PENICILLIN AND TYROTHRICIN AGAINST SULFONAMIDE-RESISTANT STRAINS. J Clin Invest. 1943 Mar;22(2):249–255. doi: 10.1172/JCI101390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. White P. J., Woods D. D. The synthesis of p-aminobenzoic acid and folic acid by staphylococci sensitive and resistant to sulphonamides. J Gen Microbiol. 1965 Aug;40(2):243–253. doi: 10.1099/00221287-40-2-243. [DOI] [PubMed] [Google Scholar]

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