Inventor(s): Wlodek Mandecki, Emanuel Goldman, Maxim Chudaev

Awarded: October 2022


Many bacterial diseases are becoming more deadly as bacteria develop resistance to treatment with antibiotics. The proposed work describes an innovative path to identifying novel antibiotics. Ternary complex formation between elongation factor EF-Tu, different aminoacylated transfer RNA molecules (aa-tRNA), and guanosine triphosphate (GTP) is fundamental for protein biosynthesis in all known microorganisms. Naturally occurring inhibitors of this step made by Streptomyces and related species suggests that this is a good target for development of antibiotics. There are no inhibitors currently in use in clinical practice that target this particular step. There are a few known inhibitors of this step that work in vitro (e.g., kirromycin), but these inhibitors have not proved to be clinically effective. By modifying E. coli EF-Tu genetically, and with attachment of fluorescent dyes to the modified EF-Tu and an E. coli tRNA-Phe molecule (Cy5 and Cy3, respectively), we have been able to demonstrate fluorescence resonance energy transfer (FRET) upon assembly of ternary complex. The modified molecules were capable of carrying out their function in protein biosynthesis normally in vitro. These reagents are thus a powerful tool for rapid HTS screening of small molecule libraries in search for compounds inhibiting ternary complex formation. One such inhibitor has already been identified and has successfully treated topical MRSA infection in a mouse model. Tests of MGC-10 stability show it to be highly stable, with no loss after 60 minutes exposure to liver microsomes in vitro.

Market Applications:

  • The commercial product is an antibiotic that belongs to a novel class of antibiotics targeting the interactions between EF-Tu and tRNA, and inhibiting protein translation in bacteria. 
  • The new class of antibiotics being discovered will provide therapy for difficult-to-treat bacterial infections, including MRSA. 
  • The new antibiotic(s) will be a prescription drug(s) used by hospitals, clinics and doctors worldwide, either as stand-alone therapy or in conjunction with other drugs.