title: Emergence of Resistance to Fungicides: The Role of Fungicide Dose.
abstract: Resistance to antimicrobial drugs allows pathogens to survive drug treatment. The time taken for a new resistant mutant to reach a population size that is unlikely to die out by chance is called "emergence time." Prolonging emergence time would delay loss of control. We investigate the effect of fungicide dose on the emergence time in fungal plant pathogens. A population dynamical model is combined with dose-response data for Zymoseptoria tritici, an important wheat pathogen. Fungicides suppress sensitive pathogen population. This has two effects. First, the rate of appearance of resistant mutants is reduced, hence the emergence takes longer. Second, more healthy host tissue becomes available for resistant mutants, increasing their chances to invade and accelerates emergence. In theory, the two competing effects may lead to a non-monotonic dependence of the emergence time on fungicide dose that exhibits a minimum. But according to field data, fungicides are unable to reduce the fungicide-sensitive population strongly enough even at high doses. Hence, for full resistance over realistic ranges of pathogen's life history and fungicide dose-response parameters, emergence time decreases monotonically with increasing dose. For partial resistance, there can be cases within a limited parameter range, when emergence decelerates at higher doses.
authors.affiliation: First author: Plant Pathology Group, Institute of Integrative Biology, ETH Zurich, LFW, Zurich, CH-8092, Switzerland; second author: ADAS, Duggleby YO17 8BP, United Kingdom; third author: Theoretical Biology, Institute of Integrative Biology, ETH Zurich, CHN, Zurich, CH-8092; and fourth author: Rothamsted Research, Harpenden, AL5 2JQ, United Kingdom.
authors.forename: Alexey
authors.initials: A
authors.lastname: Mikaberidze
authors.affiliation: First author: Plant Pathology Group, Institute of Integrative Biology, ETH Zurich, LFW, Zurich, CH-8092, Switzerland; second author: ADAS, Duggleby YO17 8BP, United Kingdom; third author: Theoretical Biology, Institute of Integrative Biology, ETH Zurich, CHN, Zurich, CH-8092; and fourth author: Rothamsted Research, Harpenden, AL5 2JQ, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Paveley
authors.affiliation: First author: Plant Pathology Group, Institute of Integrative Biology, ETH Zurich, LFW, Zurich, CH-8092, Switzerland; second author: ADAS, Duggleby YO17 8BP, United Kingdom; third author: Theoretical Biology, Institute of Integrative Biology, ETH Zurich, CHN, Zurich, CH-8092; and fourth author: Rothamsted Research, Harpenden, AL5 2JQ, United Kingdom.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bonhoeffer
authors.affiliation: First author: Plant Pathology Group, Institute of Integrative Biology, ETH Zurich, LFW, Zurich, CH-8092, Switzerland; second author: ADAS, Duggleby YO17 8BP, United Kingdom; third author: Theoretical Biology, Institute of Integrative Biology, ETH Zurich, CHN, Zurich, CH-8092; and fourth author: Rothamsted Research, Harpenden, AL5 2JQ, United Kingdom.
authors.forename: Frank
authors.initials: F
authors.lastname: van den Bosch
mesh_terms: D001203:Ascomycota / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001393:Azoles / Q000008:administration & dosage; D025141:Drug Resistance, Fungal; D005659:Fungicides, Industrial / Q000008:administration & dosage*; D054884:Host-Pathogen Interactions; D008962:Models, Theoretical; D009154:Mutation; D010935:Plant Diseases / Q000382:microbiology* / Q000517:prevention & control; D014908:Triticum / Q000382:microbiology*
chemical_list: D001393:Azoles; D005659:Fungicides, Industrial
keywords: disease control; epidemiology; fungicide resistance; host−pathogen interaction; infectious disease; mathematical model; plant pathogens