title: In Vivo Transmission of an IncA/C Plasmid in Escherichia coli Depends on Tetracycline Concentration, and Acquisition of the Plasmid Results in a Variable Cost of Fitness.
abstract: IncA/C plasmids are broad-host-range plasmids enabling multidrug resistance that have emerged worldwide among bacterial pathogens of humans and animals. Although antibiotic usage is suspected to be a driving force in the emergence of such strains, few studies have examined the impact of different types of antibiotic administration on the selection of plasmid-containing multidrug resistant isolates. In this study, chlortetracycline treatment at different concentrations in pig feed was examined for its impact on selection and dissemination of an IncA/C plasmid introduced orally via a commensal Escherichia coli host. Continuous low-dose administration of chlortetracycline at 50 g per ton had no observable impact on the proportions of IncA/C plasmid-containing E. coli from pig feces over the course of 35 days. In contrast, high-dose administration of chlortetracycline at 350 g per ton significantly increased IncA/C plasmid-containing E. coli in pig feces (P < 0.001) and increased movement of the IncA/C plasmid to other indigenous E. coli hosts. There was no evidence of conjugal transfer of the IncA/C plasmid to bacterial species other than E. coli. In vitro competition assays demonstrated that bacterial host background substantially impacted the cost of IncA/C plasmid carriage in E. coli and Salmonella. In vitro transfer and selection experiments demonstrated that tetracycline at 32 μg/ml was necessary to enhance IncA/C plasmid conjugative transfer, while subinhibitory concentrations of tetracycline in vitro strongly selected for IncA/C plasmid-containing E. coli. Together, these experiments improve our knowledge on the impact of differing concentrations of tetracycline on the selection of IncA/C-type plasmids.
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA joh04207@umn.edu.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Johnson
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Singer
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Isaacson
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Danzeisen
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lang
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Kristi
authors.initials: K
authors.lastname: Kobluk
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Rivet
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Klaudyna
authors.initials: K
authors.lastname: Borewicz
authors.affiliation: Bacterial Epidemiology and Antimicrobial Resistance Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia, USA.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Frye
authors.affiliation: Bacterial Epidemiology and Antimicrobial Resistance Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Englen
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Davies
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000032:analysis; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D022761:Gene Transfer, Horizontal / Q000187:drug effects*; D010957:Plasmids / Q000235:genetics* / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy* / Q000382:microbiology; D013752:Tetracycline / Q000008:administration & dosage* / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D013752:Tetracycline