Bacterial dihydrofolate reductase (DHFR) (DHFR)

Bacterial dihydrofolate reductase (DHFR) is a vital enzyme involved in the folate biosynthetic pathway, where it catalyzes the NADPH-dependent reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate (UniProt, 2024). Tetrahydrofolate is a critical cofactor required for the synthesis of thymidylate, purines, and several amino acids, making DHFR essential for bacterial DNA replication and cell growth (StatPearls, 2023). Because bacteria must synthesize their own folates while humans can obtain them from dietary sources, DHFR is a highly effective target for antimicrobial therapy (PubChem, 2024). Drugs such as trimethoprim bind to the bacterial enzyme with significantly higher affinity than the human isoform, providing a broad therapeutic window for treating infections (NCBI, 2023). However, the clinical utility of DHFR inhibitors is increasingly threatened by the emergence of resistance, primarily through chromosomal mutations or the acquisition of plasmid-borne resistant DHFR variants (PubMed, 1995). This target remains a cornerstone in the treatment of urinary tract, respiratory, and gastrointestinal infections (StatPearls, 2023).

Other names

Dihydrofolate reductaseFolADfrATetrahydrofolate dehydrogenaseBacterial DHFR

Competitive inhibition of the enzyme dihydrofolate reductase, which prevents the conversion of dihydrofolate to tetrahydrofolate, an essential cofactor for the synthesis of thymidine and purines (StatPearls, 2023; PubChem, 2024).