IC50: ~10-200 μM for the translocation function of the elongation factor EF-G
Fusidic acid is a steroidal antibiotic.
Fusidic acid was identified as a steroidal antibiotic produced by the fungus Fusidium conccineum.
In vitro: Resistance to fusidic acid in S. aureus strains was selected and mutations were identified in the fusA gene, which encodes EF-G. Fusidic acid could not bind to free EF-G, but rather to EF-G GTP in the complex with ribosome, suggesting that the antibiotic required a specific conformation of EF-G for binding. Biochemically, fusidic acid permited ribosome-stimulated GTP hydrolysis by EF-G, but prevented the associated conformational changes in EF-G, and therefore prevented EF-G turnover by stabilizing EF-G GDP on the ribosome. Fusidic acid did not work on eukaryotes, but sordarin was considered to similarly act on yeast EF2 and was used to assemble EF2-80S yeast ribosome complexes for cryo-EM analysis [1].
In vivo: Animal study found that fusidic acid sodium salt was well absorbed after oral administration and it could significantly reduce the diabetes incidence in BB rats. Fusidic acid sodium salt substantially accumulated more in female rats which might refult from the steroid structure of fusidin [2].
Clinical trial: Fusidic acid was first introduced into clinical use in 1962 mainly for the treatment of Staphylococcus aureus infections [1].
References:
[1] Wilson, D. N. The A-Z of bacterial translation inhibitors. Crit. Rev. Biochem. Mol. Biol. 44(6), 393-433 (2009).
[2] Hageman I, Buschard K. Antidiabetogenic effect of fusidic acid in diabetes prone BB rats: a sex-dependent organ accumulation of the drug is seen. Pharmacol Toxicol. 2002 Sep;91(3):123-8.