Topoisomerase I Inhibitor Evodiamine Acts As an Antibacterial Agent against Drug-Resistant Klebsiella pneumoniae

Topoisomerase inhibitors have been developed in a variety of clinical applications. We investigated the inhibitory effect of evodiamine on E. coli topoisomerase I, which may lead to an antibacterial effect. Evodiamine inhibits the supercoiled plasmid DNA relaxation that is catalyzed by E. coli topoisomerase I, and computer-aided docking has shown that the Arg161 and Asp551 residues of topoisomerase I interact with evodiamine. We investigated the bactericidal effect of evodiamine against multidrug-resistant Klebsiella pneumoniae. Evodiamine showed a significantly lower minimal inhibitory concentration value (MIC 128 mu g/mL) compared with antibiotics (>512 mu g/mL) against the clinical isolate of K. pneumoniae. The results suggested that evodiamine is a potential agent against drug-resistant bacteria.