A novel application of radiomimetic compounds as antibiotic drugs

This study aims to examine the potential of radiomimetic compounds as antimicrobial therapeutics, as the recent advances in radiomimetic targeting as well as rapid increase of multidrug resistant bacteria make these compounds attractive for future development.

Representative radiomimetics from each of the three major categories was examined; C-1027 and neocarzinostatin from the protein-chromophore enediyne family; Calicheamicin from the non-protein chromophore enediyne family and Bleomycin and Tallysomycin S10b from the glycopeptide family. The activity of these compounds was examined against 12 distinct bacteria species. Inhibition was determined using disc diffusion assays and a subsequent examination of minimum inhibitory concentration of a representative organism. The onset of action of the compounds was also determined by incubating the organisms with drug in liquid media, before plating, and then determining if growth occurred.

We found that the radiomimetic glycopeptides were more active against Gram-negative species, while the enediynes were more effective against Gram-positive species. The radiomimetics also maintained their rapid onset of action, working as quickly as 5 min.

Radiomimetic compounds have activity against a wide variety of microorganisms and would support the development of radiomimetic-antibody conjugates as potential antibiotics as an option against severe bacterial infections.