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. 1984 Jul;159(1):184–190. doi: 10.1128/jb.159.1.184-190.1984

Regulatory changes in the formation of chromosomal dihydrofolate reductase causing resistance to trimethoprim.

J Flensburg, O Sköld
PMCID: PMC215611  PMID: 6330028

Abstract

High resistance to trimethoprim mediated by the several hundredfold overproduction of the drug target enzyme, dihyrofolate reductase, in a clinically isolated Escherichia coli strain, 1810, was cloned onto several vector plasmids and seemed to be comprised of a single dihydrofolate reductase gene, which by DNA-DNA hybridization and restriction enzyme digestion mapping was very similar to the corresponding gene of E. coli K-12. Determination of mRNA formation in the originally isolated resistant strain and strains with cloned trimethoprim resistance determinant demonstrated an about 15-fold increase in production of dihydrofolate reductase mRNA compared with that in E. coli K-12. This was explained by the occurrence of a promoter up mutation in the resistant isolate accompanied by changes in the restriction enzyme digestion pattern found by comparison with the corresponding pattern from E. coli K-12.

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Selected References

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