Trimethoprim

Trimethoprim is a synthetic antibiotic that selectively inhibits bacterial dihydrofolate reductase. By disrupting folate metabolism, it limits bacterial growth.

Dihydrofolate reductase: An enzyme that reduces dihydrofolate to tetrahydrofolate, supporting nucleotide synthesis and other metabolic reactions. Trimethoprim binds the bacterial enzyme and blocks this step in folate recycling.
Trimethoprim-sulfamethoxazole: A fixed-dose antibiotic combination containing trimethoprim and sulfamethoxazole. The drugs block sequential steps in bacterial folate synthesis and are commonly used together.
Sulfamethoxazole: A sulfonamide antibiotic that inhibits bacterial dihydropteroate synthase, an enzyme in folate synthesis. It blocks an earlier folate-pathway step than trimethoprim and is often paired with it.
Antimicrobial resistance: The ability of microorganisms to withstand drugs that once inhibited or killed them. Rising resistance among pathogens can reduce the reliability of trimethoprim treatment.
Folate: A family of compounds that carry one-carbon units in reactions needed to synthesize nucleotides and other molecules. Trimethoprim interrupts the bacterial folate cycle that supplies DNA-building blocks.
Urinary tract infection: An infection involving the kidneys, bladder, ureters, or urethra, usually caused by bacteria. Trimethoprim is used against susceptible bacteria causing some urinary tract infections.
Pyrimethamine: An antiparasitic drug that inhibits dihydrofolate reductase in protozoa, including Plasmodium species. It targets related reductase enzymes but is used chiefly against parasites.
Dihydrofolate reductase mutation: A genetic change in dihydrofolate reductase that can alter enzyme function or susceptibility to inhibitors. Target changes can reduce trimethoprim binding while preserving bacterial folate metabolism.
Tetrahydrofolate: The reduced, metabolically active form of folate that carries one-carbon units in biosynthesis. Blocking its regeneration depletes a cofactor bacteria need to make nucleotides.
Pneumocystis pneumonia: A pneumonia caused by the fungus Pneumocystis jirovecii, especially in people with weakened immune systems. Trimethoprim-sulfamethoxazole is a standard treatment and preventive therapy for this infection.

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