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 ␤-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 ␤-lactamase upon admission to the ICU, suggesting that the AmpC ␤-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 ϳ167-kb IncA/C plasmid encoding the FOX-5 ␤-lactamase, a CARB-2 ␤-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 ␤-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.

Plasmid evolution in carbapenemase‐producing Enterobacteriaceae: a review

“…Other countries, such as Australia, Canada, and Italy, reported other plasmid types, including IncFII, IncR, IncP, and L/M, in Citrobacter spp . Recent studies have reported the increased isolation of A/C plasmids in Enterobacteriaceae species, including E. coli , K. pneumoniae , and Salmonella spp . Most isolates reported in our review here were clinical isolates from humans; few studies evaluated here addressed carbapenemases and plasmid replicon groups in animal and environmental isolates (Fig.…”

Carbapenemase-producing enterobacteriaceae recovered from a Spanish river ecosystem

“…coli : i) ST1434, previously detected in Mexico in two strains recovered from water and human feces which were categorized as non-pathogenic [34]; ii) ST216, identified among ESBL-producing E . coli strains of fecal origin in the US [35] and Europe [36], and as the most prevalent ST in IMP-producing strains recovered from gulls feces in Australia [37]; and iii) ST5001, a singleton newly described in this study. Both ST1434 and ST216 belong to clonal complex CC10, from which several KPC-producing isolates have previously been described, although only in surveillance culture studies in Israel [38].…”

Identification of IncA/C Plasmid Replication and Maintenance Genes and Development of a Plasmid Multilocus Sequence Typing Scheme

“…The first IncA/C plasmids were isolated from aquatic host species, including the fish pathogen Aeromonas salmonicida (6), and pandemic strains of Vibrio cholerae (7,8). However, recently, there has been a significant increase in the isolation of IncA/C plasmids from Enterobacteriaceae, including Salmonella (9), Klebsiella pneumoniae (10), and Escherichia coli (11).…”