Opinion | Published:

Targeting virulence: can we make evolution-proof drugs?

Nature Reviews Microbiology volume 12, pages 300308 (2014) | Download Citation

Abstract

Antivirulence drugs are a new type of therapeutic drug that target virulence factors, potentially revitalising the drug-development pipeline with new targets. As antivirulence drugs disarm the pathogen, rather than kill or halt pathogen growth, it has been hypothesized that they will generate much weaker selection for resistance than traditional antibiotics. However, recent studies have shown that mechanisms of resistance to antivirulence drugs exist, seemingly damaging the 'evolution-proof' claim. In this Opinion article, we highlight a crucial distinction between whether resistance can emerge and whether it will spread to a high frequency under drug selection. We argue that selection for resistance can be reduced, or even reversed, using appropriate combinations of target and treatment environment, opening a path towards the development of evolutionarily robust novel therapeutics.

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Acknowledgements

The authors thank D. Cornforth, P. Vale, R. Kümmerli, A. Ross-Gillespie, R. Fitzgerald and three anonymous reviewers for comments and discussion. S.P.B. was funded by the Wellcome Trust, UK (grant number WT082273), and the Engineering and Physical Sciences Research Council (EPSRC), UK (grant number EP/H032436/1). S.P.D. was funded by the Royal Society, UK, and the Natural Environment Research Council (NERC), UK (grant number NE/J007064/1). R.C.A. was funded by the Natural Environment Research Council (NERC).

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  1. School of Biological Sciences, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JY, UK.

    • Richard C. Allen
    • , Roman Popat
    •  & Sam P. Brown
  2. School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.

    • Stephen P. Diggle

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The authors declare no competing financial interests.

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Correspondence to Sam P. Brown.

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https://doi.org/10.1038/nrmicro3232

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