title: Comparative genomics of an IncA/C multidrug resistance plasmid from Escherichia coli and Klebsiella isolates from intensive care unit patients and the utility of whole-genome sequencing in health care settings.
abstract: The IncA/C plasmids have been implicated for their role in the dissemination of β-lactamases, including gene variants that confer resistance to expanded-spectrum cephalosporins, which are often the treatment of last resort against multidrug-resistant, hospital-associated pathogens. A bla(FOX-5) gene was detected in 14 Escherichia coli and 16 Klebsiella isolates that were cultured from perianal swabs of patients admitted to an intensive care unit (ICU) of the University of Maryland Medical Center (UMMC) in Baltimore, MD, over a span of 3 years. Four of the FOX-encoding isolates were obtained from subsequent samples of patients that were initially negative for an AmpC β-lactamase upon admission to the ICU, suggesting that the AmpC β-lactamase-encoding plasmid was acquired while the patient was in the ICU. The genomes of five E. coli isolates and six Klebsiella isolates containing bla(FOX-5) were selected for sequencing based on their plasmid profiles. An ∼ 167-kb IncA/C plasmid encoding the FOX-5 β-lactamase, a CARB-2 β-lactamase, additional antimicrobial resistance genes, and heavy metal resistance genes was identified. Another FOX-5-encoding IncA/C plasmid that was nearly identical except for a variable region associated with the resistance genes was also identified. To our knowledge, these plasmids represent the first FOX-5-encoding plasmids sequenced. We used comparative genomics to describe the genetic diversity of a plasmid encoding a FOX-5 β-lactamase relative to the whole-genome diversity of 11 E. coli and Klebsiella isolates that carry this plasmid. Our findings demonstrate the utility of whole-genome sequencing for tracking of plasmid and antibiotic resistance gene distribution in health care settings.
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Tracy H
authors.initials: TH
authors.lastname: Hazen
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: LiCheng
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Mallory A
authors.initials: MA
authors.lastname: Boutin
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Stancil
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Gwen
authors.initials: G
authors.lastname: Robinson
authors.affiliation: Division of Genomic Epidemiology and Clinical Outcomes, Department of Epidemiology and Public Health, Baltimore, Maryland, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harris
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Rasko
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA JKJohnson@som.umaryland.edu.
authors.forename: J Kristie
authors.initials: JK
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002511:Cephalosporins; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D007362:Intensive Care Units; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D008297:Male; D008396:Maryland; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; C094163:IncA protein, bacteria; D010750:Phosphoproteins; C444464:beta-lactamase FOX-5; D001618:beta-Lactamases