Trimethoprim primarily targets the essential bacterial enzyme, dihydrofolate reductase (DHFR), thereby inhibiting the synthesis of tetrahydrofolate, a crucial component for DNA and RNA production in susceptible microorganisms.
Mechanism of Action
Trimethoprim acts as an antimicrobial agent by specifically interfering with the folate synthesis pathway in bacteria. This pathway is vital for bacteria to produce the necessary building blocks for their genetic material and proteins.
The specific steps involved are:
- Blocking Reduction: Trimethoprim prevents the reduction of dihydrofolate to tetrahydrofolate.
- Enzyme Inhibition: This reduction is catalyzed by the enzyme dihydrofolate reductase (DHFR). Trimethoprim binds to and inhibits this enzyme in susceptible bacteria.
- Impact on Bacterial Growth: Tetrahydrofolate is essential for the synthesis of purines, pyrimidines, and certain amino acids. By blocking its production, trimethoprim effectively halts bacterial cell growth and division, leading to its antimicrobial effect.
Target Organisms
Trimethoprim's inhibitory activity extends to a range of bacteria, demonstrating its effectiveness against various common pathogens.
The types of bacteria susceptible to trimethoprim include:
Summary of Targets
For a clearer understanding, here's a summary of what trimethoprim targets:
Target Aspect | Details |
---|---|
Primary Enzyme | Dihydrofolate Reductase (DHFR) |
Metabolic Pathway | Folate synthesis, specifically the reduction of dihydrofolate to tetrahydrofolate |
Bacterial Types | Most gram-positive aerobic cocci and some gram-negative aerobic bacilli |
Significance of the Target
The mechanism by which trimethoprim works is highly effective due to its selective toxicity. Unlike bacteria, mammalian cells cannot synthesize folate and must obtain it from their diet. This fundamental difference means trimethoprim primarily targets the bacterial folate pathway, minimizing harm to human cells while effectively inhibiting bacterial growth. This selectivity makes trimethoprim a valuable antibiotic for treating various bacterial infections.