Revisiting unexploited antibiotics in search of new antibacterial drug candidates: the case of γ-actinorhodin

• Published in: Scientific reports 2017-12, Vol.7 (1), p.17419-11, Article 17419
• Main Authors: Nass, Nada M., Farooque, Sannia, Hind, Charlotte, Wand, Matthew E., Randall, Christopher P., Sutton, J. Mark, Seipke, Ryan F., Rayner, Christopher M., O’Neill, Alex J.
• Format: Article
• Language: English
• Subjects: 631/326/1320; 631/326/22/1290; Actinorhodin; Animals; Anthraquinones - pharmacology; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacterial diseases; Bactericidal activity; Candida albicans - drug effects; Cell Death - drug effects; Cell Line; Disease Models, Animal; Drug development; Drug Discovery; Drug Resistance, Bacterial; Escherichia coli - drug effects; Humanities and Social Sciences; Humans; Lactones - pharmacology; Lepidoptera; Microbial Sensitivity Tests; Mode of action; multidisciplinary; Science; Science (multidisciplinary); Staphylococcal Infections - drug therapy; Staphylococcus aureus - drug effects; Staphylococcus aureus - metabolism; Streptomyces coelicolor - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-17232-1

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.