Abstract
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.
| Original language | English |
|---|---|
| Article number | 17419 |
| Journal | Scientific Reports |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2017 |
Bibliographical note
Funding Information:This work was supported by the Medical Research Council (grant number MR/L000369/1) awarded to A.J.O., and by sponsorship from the Saudi Government and the King Abdulaziz University in Jeddah to support N.M.N. S.F. was supported by the Engineering and Physical Sciences Research Council. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Publisher Copyright:
© 2017 The Author(s).