Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-24T07:46:58.944Z Has data issue: false hasContentIssue false

Trimethoprim-resistant mutants of E. coli K12: preliminary genetic mapping

Published online by Cambridge University Press:  14 April 2009

Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Trimethoprim-resistant mutants of E. coli K12 have been isolated by-serial subculture in progressively higher concentrations of trimethoprim. High-level resistance depends on the accumulation of several mutational changes. Transduction with bacteriophage P1 has shown that all the mutations involved in resistance are associated with a locus, to be called tmr, between pyr A and pdxA and closely linked to pdxA. Resistance is accompanied by, and presumably due to, an increased activity of the target enzyme, dihydrofolate reductase. The tmr locus may include the structural gene for dihydrofolate reductase but the only mutations that have so far been observed are concerned with regulation.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1975

References

REFERENCES

Albrecht, A. M., Palmer, J. L. & Hutchinson, D. J. (1966). Differentiating properties of the dihydrofolate reductase of amethopterim-resistant Streptococcus faecalis/Ak and the sensitive parent strain. Journal of Biological Chemistry 241, 10431048.CrossRefGoogle ScholarPubMed
Berberich, R. & Levinthal, M. (1969). Mutations effecting the structure and amount of dihydrofolate reductase in Salmonella typhimurium. Bacteriological Proceedings Abstract, no. GP 71.Google Scholar
Breeze, A. S. (1972). Studies on trimethoprim-resistant mutants of Escherichia coli K12. D.Phil. thesis, University of Sussex.Google Scholar
Burchall, J. J. (1970). Purification and properties of dihydrofolate reductase from Escherichia coli. In Chemistry and Biology of Pteridines (ed. Iwai, K., Akino, M., Gots, M. and Iwanami, Y.), p. 351. Tokyo: International Academic Printing Co. Ltd.Google Scholar
Burchall, J. J. & Hitchings, G. H. (1965). Inhibitor binding analysis of dihydrofolate reductases from various species. Molecular Pharmacology 1, 126136.Google Scholar
Dempsey, W. B. & Sims, K. R. (1972). Isoleucine and threonine can prolong protein and ribonucleic acid synthesis in pyridoxine-starved mutants of Escherichia coli B. Journal of Bacteriology 112, 726735.CrossRefGoogle ScholarPubMed
Kemper, J. (1974). Gene order and co-transduction in the leu ara fol pyrA region of Salmonella typhimurium linkage map. J. Bacteriology 117, 9499.Google Scholar
Friedkin, M., Crawford, E. J. & Misra, D. (1962). Reduction of folate derivatives with dithionite in mercaptoethanol. Federation Proceedings 21, 716.Google Scholar
Poe, M., Greenfield, N. J., Hirchfield, J. M., Williams, M. N. & Hoogsteen, K. (1972). Dihydrofolate reductase. Purification and characterisation of an amethopterin resistant mutant E. coli. Biochemistry 11, 1023.CrossRefGoogle Scholar
Sirotnak, F. M. (1970). Increased dihydrofolate reductase synthesis in Diplococcus pneumoniae following translatable alteration of the structural gene. III. Further evidence on the extent of genetic involvement. Genetics 65, 391.Google Scholar
Sirotnak, F. M. (1971). High dihydrofolate reductase levels in Diplococcus pneumoniae after mutation in the structural gene: biochemical and immunological evidence for increased synthesis. Journal of Bacteriology 106, 318.Google Scholar
Sirotnak, F. M., Donati, G. J. & Hutchinson, D. J. (1964). Genetic modification of the structure and amount of dihydrofolate reductase in amethopterin-resistant Diplococcus pneumoniae. Journal of Biochemistry 239, 42984303.Google Scholar
Stacey, K. A. & Simson, E. (1965). Improved method for the isolation of thymine-requiring mutants of Escherichia coli. Journal of Bacteriology 90, 554555.CrossRefGoogle ScholarPubMed
Stowell, J. D. (1973). Studies on the effect of trimethoprim on Escherichia coli. M.Sc. thesis, University of Kent at Canterbury.Google Scholar