New antibiotics are urgently needed to treat drug-resistant bacterial pathogens. An eclectic group from Rutgers, NCATS, and Hackensack Meridian led by Wlodek Mandecki and Emanuel Goldman identified a new antibiotic compound, MGC-10, that targets the bacterial protein synthesis pathway and has broad activity against Gram-positive bacteria, including MRSA, without developing resistance. It has a MIC of 6 µM, and was harmless to mammalian cells in vitro at that concentration. MGC-10 was effective against a wide range of MRSA strains, including those resistant to the current topical antibiotic of choice, mupirocin. Extensive efforts to select for resistance to MGC-10 were unsuccessful, suggesting it may have universal antibacterial activity against S. aureus. MGC-10 was effective against MRSA in a mouse skin infection model. Although it was found to be too toxic for systemic use and is proposed as a potential topical treatment. The compound appears to work by inhibiting bacterial protein synthesis by targeting the EF-Tu protein, though its exact mechanism of action is still unclear.
Mandecki W, Chudaev M, Ye W, Wang AQ, Wilson KJ, Xu X, Kim J, Parker D, Alland D, Kumar P, Li B, Yang JH, Kreiswirth B, Mediavilla JR, Marugan JJ, Henderson MJ, Goldman E. Identification of an antibiotic from an HTS targeting EF-Tu:tRNA interaction: a prospective topical treatment for MRSA skin infections. Appl Environ Microbiol. 2025 Jan 31;91(1):e0204624. doi: 10.1128/aem.02046-24. Epub 2024 Dec 23. PMID: 39714192; PMCID: PMC11784183. https://journals.asm.org/doi/full/10.1128/aem.02046-24?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
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