title: Targeting virulence: can we make evolution-proof drugs?
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.
authors.affiliation: School of Biological Sciences, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JY, UK.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Allen
authors.affiliation: School of Biological Sciences, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JY, UK.
authors.forename: Roman
authors.initials: R
authors.lastname: Popat
authors.affiliation: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Diggle
authors.affiliation: School of Biological Sciences, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JY, UK.
authors.forename: Sam P
authors.initials: SP
authors.lastname: Brown
mesh_terms: D000890:Anti-Infective Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D005075:Biological Evolution; D004352:Drug Resistance, Microbial; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
chemical_list: D000890:Anti-Infective Agents; D037521:Virulence Factors