Trimethoprim action and its analogy with thymine starvation.

Antimicrobial agents and chemotherapy ·Vol. 5 ·No. 2 ·1974-02-00 ·Pages 169-78

Amyes SG, Smith JT

Abstract

In a minimal medium, trimethoprim is merely bacteriostatic on the prototroph Escherichia coli 114. The drug was bactericidal when the amino acids methionine and glycine, plus a purine or purine nucleoside, were also present. This response could be reversed completely when thymine and lysine were added to the culture. Methionine, glycine, and the purine are thought to maintain the integrity of the tetrahydrofolate pool under trimethoprim treatment and prevent the thymidylate synthetase reaction. Thus, the organism behaves phenotypically as a thymineless mutant. The mechanisms by which thymine and lysine reverse the bactericidal effect of trimethoprim in a minimal medium containing methionine, glycine, and adenine is discussed.

MeSH Terms

Chloramphenicol/pharmacology Culture Media Escherichia coli/enzymology,metabolism Floxuridine/pharmacology Nucleosides/pharmacology Purines/pharmacology Tetrahydrofolate Dehydrogenase/metabolism Thymine/metabolism,pharmacology Trimethoprim/antagonists & inhibitors,pharmacology

Chemicals

Culture Media Nucleosides Purines Floxuridine Chloramphenicol Trimethoprim Tetrahydrofolate Dehydrogenase Thymine

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Amyes S G

Smith J T

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29 references, click to expand

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Article Info

Journal

Antimicrobial agents and chemotherapy

Abbr.

Antimicrob Agents Chemother

ISSN

0066-4804

DOI

10.1128/AAC.5.2.169

Published

1974-02-00

Pages

169-78

Language

English

Region

United States

NLM ID

0315061

PMCID

PMC428939

Subset

External Links

PubMed source DOI: 10.1128/AAC.5.2.169 PMC Full Text View journal details

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Trimethoprim action and its analogy with thymine starvation.

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