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.

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Citation

Hazen TH, Zhao L, Boutin MA, Stancil A, Robinson G, Harris AD, Rasko DA, Johnson JK

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.

Antimicrob Agents Chemother. 2014 Aug;58(8):4814-25. doi: 10.1128/AAC.02573-14. Epub 2014 Jun 9.

PubMed ID
24914121 [ View in PubMed
]
Abstract

The IncA/C plasmids have been implicated for their role in the dissemination of beta-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 beta-lactamase upon admission to the ICU, suggesting that the AmpC beta-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 approximately 167-kb IncA/C plasmid encoding the FOX-5 beta-lactamase, a CARB-2 beta-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 beta-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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Beta-lactamaseQ93LQ9Details