Capturing Antibiotic-Resistant Ribosomes

Macrolides, lincosamides, and streptogramins (MLS) are broad-spectrum antibiotics that inhibit protein synthesis by binding to the 50S subunit of the bacterial ribosome (Fig. 1A). They are ranked “highest priority” on the World Health Organization (WHO)’s list of “Critically Important Antimicrobials for Human Medicine” (1). However, the efficacy of MLS has diminished over time due to the widespread transmission of the resistance determinant erm in almost all ESKAPE (Enterococcus faecium, Staphylococcus aureuus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are the leading causes of hospital-acquired infections (HAI). Erm-mediated MLS resistance often represent up to 60-98% of the pathogenic MLS-resistant clinical isolates, a percentage that surpasses MLS resistance caused by drug inactivation and efflux mechanisms combined (2). Erm dimethylates a single nucleotide (hereafter re