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Resistance to Trimethoprim

  • L. P. Elwell
  • M. E. Fling
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 91)

Abstract

Trimethoprim (2,4-diamino-5-(3′,4′5′-trimethoxybenzyl)pyrimidine) is one of a series of compounds first fully described by Roth et al. (1962). These compounds possess both antimalarial and antibacterial activity, the former activity exemplified by pyrimethamine and the latter activity by trimethoprim (Tp). Tp is a potent inhibitor of dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase EC 1.5.1.3; DHFR), an enzyme that catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, a cofactor required for the metabolism of some amino acids, purines and thymidine. The structure of trimethoprim and one of its clinically used structural analogs, tetroxoprim, is shown in Fig. 1. Tp has a several thousand-fold higher affinity for bacterial DHFR than for mammalian DHFR; the bacterial synthesis of tetrahydrofolate is preferentially diminished as a consequence of this selective binding (Burchall 1973; Hitchings 1973).

Keywords

Antimicrob Agent Dihydrofolate Reductase Resistance Determinant Phage Type aadA Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • L. P. Elwell
  • M. E. Fling

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