Antibiotic inhibiting ternary complex formation in ribosomal translation in Gram positive bacteria

We have identified an antibiotic drug lead, named MGC-10, which kills Gram positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), with a MIC (minimum inhibitory concentration) 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 . The target for the MGC-10 activity is the ternary complex comprised of elongation factor Tu (EF-Tu), an aminoacylated tRNA (aa-tRNA), and guanosine triphosphate (GTP). Ternary complex delivers amino acids to the growing protein chain, bringing aa-tRNA into the codon-programmed A-site of the ribosome. MGC-10 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. The drug showed little if any accumulation in the livers of topically treated mice.