1887

Abstract

Summary

Hyperproduction of the type IV plasmid-encoded dihydrofolate reductase was studied in J62-2 (pUK1123). Hyperproduction of the enzyme was shown to occur not simply as a response to a given concentration of trimethoprim but also to the presence of thymidine in the medium. Before hyperproduction occurred the bacteria began to elongate and die, thus showing the symptoms of thymine starvation. Hyperproduction also required the presence of L-methionine, adenine and glycine, suggesting that the elevated production of the enzyme was a response to the ability of trimethoprim to starve the cell of thymine metabolites.

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/content/journal/jmm/10.1099/00222615-38-4-250
1993-04-01
2024-02-21
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References

  1. Burchall JJ, Hitchings GH. Inhibitor binding analysis of dihydrofolate reductases from various species. Mol Pharmacol 1965; 1:126–136
    [Google Scholar]
  2. Amyes SGB, Smith JT. R-factor trimethoprim resistance mechanism: an insusceptible target site. Biochem Biophys Res Commun 1974; 58:412–418
    [Google Scholar]
  3. Huovinen P. Trimethoprim resistance. Antimicrob Agents Chemother 1987; 31:1451–1456
    [Google Scholar]
  4. Amyes SGB, Towner KJ. Trimethoprim resistance; epidemi ology and molecular aspects. J Med Microbiol 1990; 31:1–19
    [Google Scholar]
  5. Jansson C, Skold O. Appearance of a new trimethoprim resistance gene, dhfrIX, in Escherichia coli from swine. Antimicrob Agents Chemother 1991; 35:1891–1899
    [Google Scholar]
  6. Young H-K, Amyes SGB. A new mechanism of plasmid trimethoprim resistance: characterization of an inducible dihydrofolate reductase. J Biol Chem 1986; 261:2503–2505
    [Google Scholar]
  7. Flensburg T, Skold O. Massive overnroduction of dihydrofolate reductase in bacteria as a response to the use of trimethoprim. Eur J Biochem 1987; 162:473–176
    [Google Scholar]
  8. Smith DR, Calvo JM. Nucleotide sequence of dihydrofolate reductase genes from trimethoprim-resistant mutants of Escherichia coli. Evidence that dihydrofolate reductase interacts with another essential gene product. Mol Gen Genet 1982; 187:72–78
    [Google Scholar]
  9. Tennhammar-Ekman B, Sundstrom L, Skold O. New observa tions regarding evolution of trimethoprim resistance. J Antimicrob Chemother 1986; 18: Suppl C 67–76
    [Google Scholar]
  10. Young H-K, Jesudason MV, Koshi G, Amyes SGB. Unusual expression of new low-level-trimethoprim-resistance plasmids. J Clin Microbiol 1986; 24:61–64
    [Google Scholar]
  11. Amyes SGB, Smith JT. Trimethoprim antagonists: effect of uridine in laboratory media. J Antimicrob Chemother 1978; 4:421–129
    [Google Scholar]
  12. Davis BD, Mingioli ES. Mutants of Escherichia coli requiring methionine or vitamin B12. J Bacteriol 1950; 60:17–28
    [Google Scholar]
  13. Waddell WJ. A simple ultraviolet spectrophotometric method for the determination of protein. J Lab Clin Med 1956; 48:311–314
    [Google Scholar]
  14. Cohen SS, Barner HD. Studies on the induction of thymine deficiency and on the effects of thymine and thymidine analogues in Escherichia coli . J Bacteriol 1956; 71:588–597
    [Google Scholar]
  15. Amyes SGB, Smith JT. Trimethoprim action and its analogy with thymine starvation. Antimicrob Agents Chemother 1974; 5:169–178
    [Google Scholar]
  16. Hitchings GH. Functions of tetrahydrofolate and the role of dihydrofolate reductase in cellular metabolism. In Hitchings GH. ed Handbook of experimental pharmacology. Inhibition of folate metabolism in chemotherapy. The origins and uses of co-trimoxazole. Chapter 64. Berlin: Springer-Verlag; 1983:11–23
    [Google Scholar]
  17. Cohen SS, Barner H. Enzymatic adaption in a thymine requiring strain of Escherichia coli. J Bacteriol 1955; 69:59–66
    [Google Scholar]
  18. Thomson CJ, Young H-K, Amyes SGB. N-terminal amino-acid sequence and subunit structure of the type IV trimethoprim-resistant plasmid-encoded dihydrofolate reductase. J Med Microbiol 1990; 32:153–158
    [Google Scholar]
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