title: WGS accurately predicts antimicrobial resistance in Escherichia coli.
abstract: OBJECTIVE
  The objective of this study was to determine the effectiveness of WGS in identifying resistance genotypes of MDR Escherichia coli and whether these correlate with observed phenotypes.
  
  
  METHODS
  Seventy-six E. coli strains were isolated from farm cattle and measured for phenotypic resistance to 15 antimicrobials with the Sensititre(®) system. Isolates with resistance to at least four antimicrobials in three classes were selected for WGS using an Illumina MiSeq. Genotypic analysis was conducted with in-house Perl scripts using BLAST analysis to identify known genes and mutations associated with clinical resistance.
  
  
  RESULTS
  Over 30 resistance genes and a number of resistance mutations were identified among the E. coli isolates. Resistance genotypes correlated with 97.8% specificity and 99.6% sensitivity to the identified phenotypes. The majority of discordant results were attributable to the aminoglycoside streptomycin, whereas there was a perfect genotype-phenotype correlation for most antibiotic classes such as tetracyclines, quinolones and phenicols. WGS also revealed information about rare resistance mechanisms, such as structural mutations in chromosomal copies of ampC conferring third-generation cephalosporin resistance.
  
  
  CONCLUSIONS
  WGS can provide comprehensive resistance genotypes and is capable of accurately predicting resistance phenotypes, making it a valuable tool for surveillance. Moreover, the data presented here showing the ability to accurately predict resistance suggest that WGS may be used as a screening tool in selecting anti-infective therapy, especially as costs drop and methods improve.
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Tyson
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McDermott
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Yuansha
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Tadesse
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Sampa
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Sonya
authors.initials: S
authors.lastname: Bodeis-Jones
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Claudine
authors.initials: C
authors.lastname: Kabera
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Gaines
authors.affiliation: International Center for Food Industry Excellence, Department of Animal and Food Sciences, Texas Tech University, Lubbock, TX, USA.
authors.forename: Guy H
authors.initials: GH
authors.lastname: Loneragan
authors.affiliation: Food and Feed Safety Research Unit, Agricultural Research Service, US Department of Agriculture, College Station, TX, USA.
authors.forename: Tom S
authors.initials: TS
authors.lastname: Edrington
authors.affiliation: Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Torrence
authors.affiliation: US Meat Animal Research Center, Agricultural Research Service, US Department of Agriculture, Clay Center, NE, USA.
authors.forename: Dayna M
authors.initials: DM
authors.lastname: Harhay
authors.affiliation: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD, USA shaohua.zhao@fda.hhs.gov.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002417:Cattle; D002418:Cattle Diseases / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D004927:Escherichia coli Infections / Q000662:veterinary*; D029968:Escherichia coli Proteins / Q000235:genetics; D023061:Gene Order; D056726:Genetic Association Studies; D016680:Genome, Bacterial; D005838:Genotype; D008826:Microbial Sensitivity Tests; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins