gamma-actinorhodin and Disease-Models--Animal

Of the thousands of natural product antibiotics discovered to date, only a handful have been developed for the treatment of bacterial infection. The clinically unexploited majority likely include compounds with untapped potential as antibacterial drugs, and in view of the ever-growing unmet medical need for such agents, warrant systematic re-evaluation. Here we revisit the actinorhodins, a class that was first reported 70 years ago, but which remains poorly characterized. We show that γ-actinorhodin possesses many of the requisite properties of an antibacterial drug, displaying potent and selective bactericidal activity against key Gram-positive pathogens (including Staphylococcus aureus and enterococci), a mode of action distinct from that of other agents in clinical use, an extremely low potential for the development of resistance, and a degree of in vivo efficacy in an invertebrate model of infection. Our findings underscore the utility of revisiting unexploited antibiotics as a source of novel antibacterial drug candidates.

Topics: Animals; Anthraquinones; Anti-Bacterial Agents; Candida albicans; Cell Death; Cell Line; Disease Models, Animal; Drug Discovery; Drug Resistance, Bacterial; Escherichia coli; Humans; Lactones; Lepidoptera; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Streptomyces coelicolor