title: Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter spp.
abstract: The objectives of this study were to identify antimicrobial resistance genotypes for Campylobacter and to evaluate the correlation between resistance phenotypes and genotypes using in vitro antimicrobial susceptibility testing and whole-genome sequencing (WGS). A total of 114 Campylobacter species isolates (82 C. coli and 32 C. jejuni) obtained from 2000 to 2013 from humans, retail meats, and cecal samples from food production animals in the United States as part of the National Antimicrobial Resistance Monitoring System were selected for study. Resistance phenotypes were determined using broth microdilution of nine antimicrobials. Genomic DNA was sequenced using the Illumina MiSeq platform, and resistance genotypes were identified using assembled WGS sequences through blastx analysis. Eighteen resistance genes, including tet(O), blaOXA-61, catA, lnu(C), aph(2″)-Ib, aph(2″)-Ic, aph(2')-If, aph(2″)-Ig, aph(2″)-Ih, aac(6')-Ie-aph(2″)-Ia, aac(6')-Ie-aph(2″)-If, aac(6')-Im, aadE, sat4, ant(6'), aad9, aph(3')-Ic, and aph(3')-IIIa, and mutations in two housekeeping genes (gyrA and 23S rRNA) were identified. There was a high degree of correlation between phenotypic resistance to a given drug and the presence of one or more corresponding resistance genes. Phenotypic and genotypic correlation was 100% for tetracycline, ciprofloxacin/nalidixic acid, and erythromycin, and correlations ranged from 95.4% to 98.7% for gentamicin, azithromycin, clindamycin, and telithromycin. All isolates were susceptible to florfenicol, and no genes associated with florfenicol resistance were detected. There was a strong correlation (99.2%) between resistance genotypes and phenotypes, suggesting that WGS is a reliable indicator of resistance to the nine antimicrobial agents assayed in this study. WGS has the potential to be a powerful tool for antimicrobial resistance surveillance programs.
authors.affiliation: Division of Animal and Food Microbiology Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA shaohua.zhao@fda.hhs.gov.
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Division of Animal and Food Microbiology Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Tyson
authors.affiliation: Division of Animal and Food Microbiology Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Animal and Food Microbiology Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Animal and Food Microbiology Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Animal and Food Microbiology Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
authors.forename: S
authors.initials: S
authors.lastname: Young
authors.affiliation: Division of Animal and Food Microbiology Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lam
authors.affiliation: Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Folster
authors.affiliation: Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Whichard
authors.affiliation: Division of Animal and Food Microbiology Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: McDermott
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002167:Campylobacter / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D002169:Campylobacter Infections / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D005516:Food Microbiology; D016680:Genome, Bacterial; D006801:Humans; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins