title: Mathematical modelling of antimicrobial resistance in agricultural waste highlights importance of gene transfer rate.
abstract: Antimicrobial resistance is of global concern. Most antimicrobial use is in agriculture; manures and slurry are especially important because they contain a mix of bacteria, including potential pathogens, antimicrobial resistance genes and antimicrobials. In many countries, manures and slurry are stored, especially over winter, before spreading onto fields as organic fertilizer. Thus, these are a potential location for gene exchange and selection for resistance. We develop and analyse a mathematical model to quantify the spread of antimicrobial resistance in stored agricultural waste. We use parameters from a slurry tank on a UK dairy farm as an exemplar. We show that the spread of resistance depends in a subtle way on the rates of gene transfer and antibiotic inflow. If the gene transfer rate is high, then its reduction controls resistance, while cutting antibiotic inflow has little impact. If the gene transfer rate is low, then reducing antibiotic inflow controls resistance. Reducing length of storage can also control spread of resistance. Bacterial growth rate, fitness costs of carrying antimicrobial resistance and proportion of resistant bacteria in animal faeces have little impact on spread of resistance. Therefore, effective treatment strategies depend critically on knowledge of gene transfer rates.
authors.affiliation: School of Biosciences, University of Nottingham, Loughborough, LE12 5RD, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Baker
authors.affiliation: School of Biosciences, University of Nottingham, Loughborough, LE12 5RD, UK.
authors.forename: Jon L
authors.initials: JL
authors.lastname: Hobman
authors.affiliation: School of Biosciences, University of Nottingham, Loughborough, LE12 5RD, UK.
authors.forename: Christine E R
authors.initials: CE
authors.lastname: Dodd
authors.affiliation: School of Biosciences, University of Nottingham, Loughborough, LE12 5RD, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ramsden
authors.affiliation: School of Biosciences, University of Nottingham, Loughborough, LE12 5RD, UK dov.stekel@nottingham.ac.uk.
authors.forename: Dov J
authors.initials: DJ
authors.lastname: Stekel
mesh_terms: D000383:Agriculture; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D022761:Gene Transfer, Horizontal / Q000235:genetics*; D008372:Manure / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical
chemical_list: D000900:Anti-Bacterial Agents; D008372:Manure
keywords: AMR; antimicrobial resistance; dairy slurry; horizontal gene transfer; mathematical model