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

Nada M. Nass, Sannia Farooque, Charlotte Hind, Matthew Wand, Christopher P. Randall, J. Mark Sutton, Ryan F. Seipke, Christopher M. Rayner, Alex J. O'Neill*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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 languageEnglish
Article number17419
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 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).

Fingerprint

Dive into the research topics of 'Revisiting unexploited antibiotics in search of new antibacterial drug candidates: The case of γ-actinorhodin'. Together they form a unique fingerprint.

Cite this