Targeting Virulence: Can We Make Evolution-Proof Drugs?

Nat Rev Microbiol. 2014 Apr;12(4):300-8. doi: 10.1038/nrmicro3232.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Infective Agents / isolation & purification*
  • Anti-Infective Agents / pharmacology*
  • Biological Evolution*
  • Drug Resistance, Microbial
  • Virulence / drug effects
  • Virulence Factors / antagonists & inhibitors*

Substances

  • Anti-Infective Agents
  • Virulence Factors