title: Comparative genomics of multidrug resistance-encoding IncA/C plasmids from commensal and pathogenic Escherichia coli from multiple animal sources.
abstract: Incompatibility group A/C (IncA/C) plasmids have received recent attention for their broad host range and ability to confer resistance to multiple antimicrobial agents. Due to the potential spread of multidrug resistance (MDR) phenotypes from foodborne pathogens to human pathogens, the dissemination of these plasmids represents a public health risk. In this study, four animal-source IncA/C plasmids isolated from Escherichia coli were sequenced and analyzed, including isolates from commercial dairy cows, pigs and turkeys in the U.S. and Chile. These plasmids were initially selected because they either contained the floR and tetA genes encoding for florfenicol and tetracycline resistance, respectively, and/or the bla(CMY-2) gene encoding for extended spectrum β-lactamase resistance. Overall, sequence analysis revealed that each of the four plasmids retained a remarkably stable and conserved backbone sequence, with differences observed primarily within their accessory regions, which presumably have evolved via horizontal gene transfer events involving multiple modules. Comparison of these plasmids with other available IncA/C plasmid sequences further defined the core and accessory elements of these plasmids in E. coli and Salmonella. Our results suggest that the bla(CMY-2) plasmid lineage appears to have derived from an ancestral IncA/C plasmid type harboring floR-tetAR-strAB and Tn21-like accessory modules. Evidence is mounting that IncA/C plasmids are widespread among enteric bacteria of production animals and these emergent plasmids have flexibility in their acquisition of MDR-encoding modules, necessitating further study to understand the evolutionary mechanisms involved in their dissemination and stability in bacterial populations.
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, United States of America.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fernández-Alarcón
authors.forename: Randall S
authors.initials: RS
authors.lastname: Singer
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017920:Antiporters / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002417:Cattle; D002677:Chile; D016000:Cluster Analysis; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics; D023061:Gene Order; D022761:Gene Transfer, Horizontal; D023281:Genomics / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D010957:Plasmids / Q000145:classification / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013552:Swine; D013753:Tetracycline Resistance / Q000235:genetics; D013839:Thiamphenicol / Q000031:analogs & derivatives / Q000494:pharmacology; D014422:Turkeys; D014481:United States; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D017920:Antiporters; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C501927:FloR protein, E coli; C079051:tetA protein, Bacteria; C035534:florfenicol; C103022:beta-lactamase CMY-2; D001618:beta-Lactamases; D013839:Thiamphenicol