High throughput screening identifies potential inhibitors targeting trimethoprim resistant DfrA1 protein in Klebsiella pneumoniae and Escherichia coli.

The DfrA1 protein provides trimethoprim resistance in bacteria, especially Klebsiella pneumoniae and Escherichia coli, by modifying dihydrofolate reductase, which reduces the binding efficacy of the antibiotic. This study identified inhibitors of the trimethoprim-resistant DfrA1 protein through high-throughput computational screening and optimization of 3,601 newly synthesized chemical compounds from the ChemDiv database, aiming to discover potential drug candidates targeting DfrA1 in K. pneumoniae and E.