Cresomycin by-passes the erm genes to exhibit anti-bacterial activity against multiantibiotic-resistant Staphylococcus aureus

Multi-antibiotic resistant Staphylococcus aureus (MARSA) develops resistance against several antibiotics because of erm (erythromycin ribosome methylase) gene, which encodes rRNA adenine N-6-methyltransferase (RAMT). Dimethylation to the nucleotide A2058 of the 23S rRNA within the 50S ribosomal subunit by RAMT. The methylation of A2058 prevents the antibiotics binding to 23S subunit of the bacterial ribosomes allowing bacterial protein synthesis thereby promoting anti-bacterial resistance. We have performed a recent literature review to identify the potential drugs/drug-like candidates that overcome the anti-bacterial resistance caused by erm gene against MARSA. Recent studies suggest that Cresomycin is a novel synthetic lincosamide antibiotic developed to address the growing challenge of antimicrobial resistance, particularly among MARSA. Structurally, cresomycin retains the bicyclic oxepanopolinamide residue characteristic of iboxamycin while incorporating a thiolincosamine moiety that forms a unique 10-membered ring, a structural modification that enhances ribosomal binding affinity and improves stability against metabolic degradation. Mechanistically, cresomycin inhibits bacterial protein synthesis through binding to the 50S ribosomal subunit and demonstrates broad antimicrobial activity against gram-positive and gram-negative bacteria. Structural analyses suggest that cresomycin is pre-organized and binds to ribosomes even after methylation by RAMT. Overall, current evidence suggests that cresomycin is a promising next-generation antibiotic against resistant bacterial pathogens, pending further clinical trials.