Virtual Screening and Experimental Verification to Identify Potential Inhibitors of the ErmC Methyltransferase Responsible for Bacterial Resistance Against Macrolide Antibiotics

Methyltransferases from the Erm family catalyze S-adenosyl-L-methionine-dependent modification of a specific adenine residue in bacterial 23S rRNA, thereby conferring resistance to clinically important macrolide, lincosamide, and streptogramin B antibiotics. Thus far, no inhibitors of these enzymes have been identified or designed that would effectively abolish theresistance in vivo. We used the crystal structure of ErmC’ methyltransferase as a target for structure-based virtual screening of a database composed of 58,679 lead-like compounds.