Please read Dr. Goldman’s article in Applied and Environmental Microbiology titled, “Identification of an antibiotic from an HTS targeting EF-Tu:tRNA interaction: a prospective topical treatment for MRSA skin infections.“
Because of the urgent need for new antibiotics to treat drug-resistant bacterial pathogens, we employed an assay that rapidly screens large quantities of compounds for their ability to interfere with bacterial protein synthesis, in particular, the delivery of amino acids to the ribosome via tRNA and elongation factor Tu (EF-Tu). We have identified a drug lead, named MGC-10, which kills Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), with a MIC of 6 µM, while being harmless to mammalian cells in vitro in that concentration range. The antibacterial activity of MGC-10 was broad against over 50 strains of antibiotic-resistant samples obtained from hospital infections, where MGC-10 inhibited all tested strains of MRSA. Extensive selection and screening with MGC-10 did not yield any resistant strains, indicating it may have universal antibacterial activity against S. aureus. Pharmacokinetics performed in mice suggested that MGC-10 was too toxic for systemic use; however, it appears to have potential as a topical treatment for difficult-to-treat wounds or skin infections by Gram-positive pathogens such as MRSA. In a mouse skin-infection model with MRSA, MGC-10 performed as well or better than the present topical drug of choice, mupirocin. MGC-10 showed little, if any, accumulation in the livers of topically treated mice. These results bode well for the future use of MGC-10 in clinical application as it could be used to treat a broad range of S. aureus skin infections that are resistant to known antibiotics. To read the full article.
Identification of an antibiotic from an HTS targeting EF-Tu:tRNA interaction: a prospective topical treatment for MRSA skin infections. 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. Appl Environ Microbiol. 2024 Dec 23:e0204624. PMID: 39714192 DOI: 1128/aem.02046-24