Affiliation:
1. Department of Pharmaceutics, The School of Pharmacy, University of London, Brunswick Square, London, WC1N 1AX, United Kingdom
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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