title: Is selection relevant in the evolutionary emergence of drug resistance?
abstract: The emergence of drug-resistant pathogens is often considered a canonical case of evolution by natural selection. Here we argue that the strength of selection can be a poor predictor of the rate of resistance emergence. It is possible for a resistant strain to be under negative selection and still emerge in an infection or spread in a population. Measuring the right parameters is a necessary first step toward the development of evidence-based resistance-management strategies. We argue that it is the absolute fitness of the resistant strains that matters most and that a primary determinant of the absolute fitness of a resistant strain is the ecological context in which it finds itself.
authors: Department of Mathematics and Statistics, Jeffery Hall, Queen's University, Kingston, ON K7L 3N6, Canada; Department of Biology, Queen's University, Kingston, ON K7L 3N6, Canada; The Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tday@mast.queensu.ca.
authors: Troy
authors: T
authors: Day
authors: ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors: Silvie
authors: S
authors: Huijben
authors: The Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA; Center for Infectious Disease Dynamics, Departments of Biology and Entomology, Pennsylvania State University, University Park, PA 16802, USA.
authors: Andrew F
authors: AF
authors: Read
mesh_terms: D004351:Drug Resistance / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D019143:Evolution, Molecular; D056084:Genetic Fitness; D009154:Mutation; D016788:Plasmodium chabaudi / Q000187:drug effects / Q000235:genetics; D012641:Selection, Genetic
keywords: antibiotics; chemotherapy; evolutionary rescue; mutant selection window