Multiple Variants of <i>Klebsiella pneumoniae</i> Producing Carbapenemase in One Patient

Mulvey, Michael R.; Haraoui, Louis-Patrick; Longtin, Yves

doi:10.1056/nejmc1511360

Cited by 9 publications

(12 citation statements)

References 5 publications

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“…The observation of HGT within a single patient is remarkable and has broad implications for the emergence of new infectious diseases. A single person was infected with multiple strains of carbapenem-resistant Klebsiella and Escherichia, and researchers were able to reconstruct the transmission events where conjugation transferred the bla KPC-3 resistance gene between bacterial species residing in the human host (Mulvey et al 2016). The same bla KPC-3 carbapenemase gene was situated within three transposon variants that differed by a single nucleotide and a 100 bp deletion.…”

Section: Conjugation Mobilizes Plasmid-borne Args In Clinical Environmentioning

confidence: 99%

“…The same bla KPC-3 carbapenemase gene was situated within three transposon variants that differed by a single nucleotide and a 100 bp deletion. One of these transposons jumped between two different plasmid incompatibility groups and across multiple strains of K. pneumoniae and E. coli (Mulvey et al 2016). DNA sequencing revealed single nucleotide variants of bla KPC-3 , which enabled reconstruction of the transmission events that spread the transposon and plasmids between organisms in the infected individual over time (Mulvey et al 2016).…”

Section: Conjugation Mobilizes Plasmid-borne Args In Clinical Environmentioning

confidence: 99%

“…After a plasmid arrives in a new host cell, plasmidborne transposable elements can further mobilize ARGs by copying them to a different plasmid or to the chromosome (Valenzuela et al 2007;Bennett 2008;Skipper et al 2013;Conlan et al 2014;Mulvey et al 2016;Ludden et al 2017). Thus, transposons create another transmission dynamic in which an ARG in a transposon can transfer to different plasmids and so increase the potential of the ARG to transmit to additional bacterial recipients through conjugation.…”

Section: Horizontal Transfer Of Accessory Resistance Cassettes Comparmentioning

confidence: 99%

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Horizontal transfer of antibiotic resistance genes in clinical environments

2019

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A global medical crisis is unfolding as antibiotics lose effectiveness against a growing number of bacterial pathogens. Horizontal gene transfer (HGT) contributes significantly to the rapid spread of resistance, yet the transmission dynamics of genes that confer antibiotic resistance are poorly understood. Multiple mechanisms of HGT liberate genes from normal vertical inheritance. Conjugation by plasmids, transduction by bacteriophages, and natural transformation by extracellular DNA each allow genetic material to jump between strains and species. Thus, HGT adds an important dimension to infectious disease whereby an antibiotic resistance gene (ARG) can be the agent of an outbreak by transferring resistance to multiple unrelated pathogens. Here, we review the small number of cases where HGT has been detected in clinical environments. We discuss differences and synergies between the spread of plasmid-borne and chromosomal ARGs, with a special consideration of the difficulties of detecting transduction and transformation by routine genetic diagnostics. We highlight how 11 of the top 12 priority antibiotic-resistant pathogens are known or predicted to be naturally transformable, raising the possibility that this mechanism of HGT makes significant contributions to the spread of ARGs. HGT drives the evolution of untreatable “superbugs” by concentrating ARGs together in the same cell, thus HGT must be included in strategies to prevent the emergence of resistant organisms in hospitals and other clinical settings.

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Section: Conjugation Mobilizes Plasmid-borne Args In Clinical Environmentioning

confidence: 99%

Section: Conjugation Mobilizes Plasmid-borne Args In Clinical Environmentioning

confidence: 99%

Section: Horizontal Transfer Of Accessory Resistance Cassettes Comparmentioning

confidence: 99%

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Horizontal transfer of antibiotic resistance genes in clinical environments

2019

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“…A recent study found over 150 distinct phylogenetic lineages of this pathogen and suggested that more remain to be identified (25). Many of these lineages can be found within a single hospital (26,27) and even within an individual patient (28), yet genotyping studies indicate that a relatively small number of lineages are responsible for a disproportionately large number of pneumonia cases (25,(29)(30)(31). For example, multilocus sequence typing has indicated that sequence type 11 (ST11), ST14, ST15, ST42, ST43, ST258, ST340, ST416, and ST512 strains are frequent causes of pneumonia over large geographic regions (25).…”

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confidence: 99%

A Genomic Approach To Identify Klebsiella pneumoniae and Acinetobacter baumannii Strains with Enhanced Competitive Fitness in the Lungs during Multistrain Pneumonia

et al. 2019

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Microbial competition is most often studied at the genus or species level, but interstrain competition has been less thoroughly examined. Klebsiella pneumoniae is an important pathogen in the context of hospital-acquired pneumonia, and a better understanding of strain competition in the lungs could explain why some strains of this bacterium are more frequently isolated from pneumonia patients than others. We developed a barcode-free method called "StrainSeq" to simultaneously track the abundances of 10 K. pneumoniae strains in a murine pneumonia model. We demonstrate that one strain (KPPR1) repeatedly achieved a marked numerical dominance at 20 h postinoculation during pneumonia but did not exhibit a similar level of dominance in in vitro mixed-growth experiments. The emergence of a single dominant strain was also observed with a second respiratory pathogen, Acinetobacter baumannii, indicating that the phenomenon was not unique to K. pneumoniae. When KPPR1 was removed from the inoculum, a second strain emerged to achieve high numbers in the lungs, and when KPPR1 was introduced into the lungs 1 h after the other nine strains, it no longer exhibited a dominant phenotype. Our findings indicate that certain strains of K. pneumoniae have the ability to outcompete others in the pulmonary environment and cause severe pneumonia and that a similar phenomenon occurs with A. baumannii. In the context of the pulmonary microbiome, interstrain competitive fitness may be another factor that influences the success and spread of certain lineages of these hospital-acquired respiratory pathogens.

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“…Our data is consistent with the frequent identification of <10 SNVs between intrapatient K. pneumoniae isolates from gastrointestinal and extraintestinal sites over similar time frames (Gorrie et al, 2017). Another study looking at the evolution of carbapenemase-producing K. pneumoniae isolates from a single patient demonstrated between 3 and 38 SNV differences over months to years (Mulvey et al, 2016). WGS could potentially still be valuable in prospective, single-patient pathogen tracking if selective pressures of given niches are greatly increased above baseline, if other pathogenic species exhibit increased mutation rates within the host, or if the duration of organism collection were extended.…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing of Klebsiella pneumoniae Isolates to Track Strain Progression in a Single Patient With Recurrent Urinary Tract Infection

Wylie

Minx

et al. 2019

Front. Cell. Infect. Microbiol.

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Klebsiella pneumoniae is an important uropathogen that increasingly harbors broad-spectrum antibiotic resistance determinants. Evidence suggests that some same-strain recurrences in women with frequent urinary tract infections (UTIs) may emanate from a persistent intravesicular reservoir. Our objective was to analyze K. pneumoniae isolates collected over weeks from multiple body sites of a single patient with recurrent UTI in order to track ordered strain progression across body sites, as has been employed across patients in outbreak settings. Whole-genome sequencing of 26 K. pneumoniae isolates was performed utilizing the Illumina platform. PacBio sequencing was used to create a refined reference genome of the original urinary isolate (TOP52). Sequence variation was evaluated by comparing the 26 isolate sequences to the reference genome sequence. Whole-genome sequencing of the K. pneumoniae isolates from six different body sites of this patient with recurrent UTI demonstrated 100% chromosomal sequence identity of the isolates, with only a small P2 plasmid deletion in a minority of isolates. No single nucleotide variants were detected. The complete absence of single-nucleotide variants from 26 K. pneumoniae isolates from multiple body sites collected over weeks from a patient with recurrent UTI suggests that, unlike in an outbreak situation with strains collected from numerous patients, other methods are necessary to discern strain progression within a single host over a relatively short time frame.

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Multiple Variants of Klebsiella pneumoniae Producing Carbapenemase in One Patient

Cited by 9 publications

References 5 publications

Horizontal transfer of antibiotic resistance genes in clinical environments

Horizontal transfer of antibiotic resistance genes in clinical environments

A Genomic Approach To Identify Klebsiella pneumoniae and Acinetobacter baumannii Strains with Enhanced Competitive Fitness in the Lungs during Multistrain Pneumonia

Whole-Genome Sequencing of Klebsiella pneumoniae Isolates to Track Strain Progression in a Single Patient With Recurrent Urinary Tract Infection

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