DNA Aptamers Mediated Inhibition of Pathogenic Erm42 Enzyme Involved in Antimicrobial Resistance

Ribosomal RNA (rRNA) modification at a specific site is a prevalent resistance mechanism utilized by multidrug-resistant pathogens, leading to antimicrobial resistance (AMR). The erythromycin-resistant methyltransferase (Erm) methylates rRNA at the conserved A2058 position, imparting resistance to a broad class of antibiotics, including macrolides, lincosamides, and streptogramin B (MLS_B). However, inhibitors that are highly specific to Erm are scarce in the literature. Herein, we report high-affinity DNA aptamers discovered through in vitro selection that target pathogenic Erm42. The aptamers, Apt-E1 and Apt-E2, displayed nanomolar binding affinity for Erm42 and effectively inhibited the Erm42-mediated methylation of rRNA. Using DNase I footprinting assays, truncated versions of Apt-E1 and Apt-E2 were engineered. They exhibited comparable binding as well as enhanced specificity toward Erm42 when compared to other methyltransferases and DNA-binding proteins. This study provides a novel DNA aptamer-based strategy, paving the way for the development of aptamer-based therapeutic and diagnostic tools to combat AMR.