A 4.5-Year Within-Patient Evolution of a Colistin-Resistant Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae Sequence Type 258

Jousset, Agnès B; Bonnin, Rémy A.; Rosinski‐Chupin, Isabelle; Girlich, Delphine; Cuzon, Gaëlle; Cabanel, Nicolas; Frech, Hélène; Farfour, Éric; Dortet, Laurent; Glaser, Philippe; Naas, Thierry

doi:10.1093/cid/ciy293

Cited by 46 publications

(46 citation statements)

References 37 publications

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“…Adaptive mutations likely contribute to ST258 persistence among hospitalized patients. In a recent study investigating CRKP ST258 colonization in a single patient, multiple adaptive mutations were identified over a 4.5-year period that resulted in increased virulence and drug resistance (29). Several of the mutated genes identified in that study, including pfeA and rcsA , were also mutated in subclade F isolates.…”

Section: Discussionmentioning

confidence: 99%

Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years

Marsh

Mustapha

Griffith

et al. 2019

mBio

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Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains belonging to sequence type 258 (ST258) are frequent causes of hospital-associated outbreaks and are a major contributor to the spread of carbapenemases. This genetic lineage emerged several decades ago and remains a major global health care challenge. In this study, genomic epidemiology was used to investigate the emergence, evolution, and persistence of ST258 carbapenem-resistant K. pneumoniae outbreak-causing lineages at a large tertiary care hospital over 8 years. A time-based phylogenetic analysis of 136 ST258 isolates demonstrated the succession of multiple genetically distinct ST258 sublineages over the 8-year period. Ongoing genomic surveillance identified the emergence and persistence of several distinct clonal ST258 populations. Patterns of multidrug resistance determinants and plasmid replicons were consistent with continued evolution and persistence of these populations. Five ST258 outbreaks were documented, including three that were caused by the same clonal lineage. Mutations in genes encoding effectors of biofilm production and iron acquisition were identified among persistent clones. Two emergent lineages bearing K. pneumoniae integrative conjugative element 10 (ICEKp10) and harboring yersiniabactin and colibactin virulence factors were identified. The results show how distinct ST258 subpopulations have evolved and persisted within the same hospital over nearly a decade. IMPORTANCE The carbapenem class of antibiotics is invaluable for the treatment of selected multidrug-resistant Gram-negative pathogens. The continued transmission of carbapenem-resistant bacteria such as ST258 K. pneumoniae is of serious global public health concern, as treatment options for these infections are limited. This genomic epidemiologic investigation traced the natural history of ST258 K. pneumoniae in a single health care setting over nearly a decade. We found that distinct ST258 subpopulations have caused both device-associated and ward-associated outbreaks, and some of these populations remain endemic within our hospital to the present day. The finding of virulence determinants among emergent ST258 clones supports the idea of convergent evolution of drug-resistant and virulent CRKP strains and highlights the need for continued surveillance, prevention, and control efforts to address emergent and evolving ST258 populations in the health care setting.

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Section: Discussionmentioning

confidence: 99%

Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years

Marsh

Mustapha

Griffith

et al. 2019

mBio

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“…The MLST International clone ST-258 has been recognized as the prevalent ST of carbapenem-resistant K. pneumoniae isolates worldwide [45,46,47,48]. Herein, we described an isolate that belongs to sequence type ST-14 which has been associated with pan resistant isolates and the production of OXA-48 and NDM carbapenemases with a higher colistin rate of resistance when compared with isolates outside the cluster (37.1% vs. 27.1%) [49].…”

Section: Discussionmentioning

confidence: 99%

First Description of Colistin and Tigecycline-Resistant Acinetobacter baumannii Producing KPC-3 Carbapenemase in Portugal

et al. 2018

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Herein, we describe a case report of carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae isolates that were identified from the same patient at a Tertiary University Hospital Centre in Portugal. Antimicrobial susceptibility and the molecular characterization of resistance and virulence determinants were performed. PCR screening identified the presence of the resistance genes blaKPC-3, blaTEM-1 and blaSHV-1 in both isolates. The KPC-3 K. pneumoniae isolate belonged to the ST-14 high risk clone and accumulated an uncommon resistance and virulence profile additional to a horizontal dissemination capacity. In conclusion, the molecular screening led to the first identification of the A. baumannii KPC-3 producer in Portugal with a full antimicrobial resistance profile including tigecycline and colistin.

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“…Plasmid pBIC1a is a bla KPC−2 -encoding plasmid of 170,415 bp in-size from a ST258 K. pneumoniae BIC-1 (Jousset et al, 2018). This isolate was recovered from a contaminated endoscope in France in 2009 (Naas et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently, pKpQIL-like plasmids seemed to have played a major role in KPC dissemination with several reports worldwide (Baraniak et al, 2011; García-Fernández et al, 2012; Hidalgo-Grass et al, 2012; Chen et al, 2013, 2014a; Papagiannitsis et al, 2016; Doumith et al, 2017). Complete sequencing of KPC-associated plasmids revealed their plasticity with multiple rearrangements that occurred between pKpQIL-like plasmids and pKPN3, a non-KPC-encoding IncFII K1 -FIB plasmid described in K. pneumoniae MGH78578 (also known as ATCC 700721; Chen et al, 2013; Jousset et al, 2018). However, little is known about their basic biology, and due to the presence of multiple antimicrobial resistance genes on IncFII K plasmids, their broad host range, and their rapid dissemination, there is a need to understand the mechanisms underlying regulation and maintenance of these plasmids.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Landscape of a blaKPC-2 Plasmid and Response to Imipenem Exposure in Escherichia coli TOP10

et al. 2018

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The diffusion of KPC-2 carbapenemase is closely related to the spread of Klebsiella pneumoniae of the clonal-group 258 and linked to IncFIIK plasmids. Little is known about the biology of multi-drug resistant plasmids and the reasons of their successful dissemination. Using E. coli TOP10 strain harboring a multi-replicon IncFIIK-IncFIB blaKPC−2-gene carrying plasmid pBIC1a from K. pneumoniae ST-258 clinical isolate BIC-1, we aimed to identify basal gene expression and the effects of imipenem exposure using whole transcriptome approach by RNA sequencing (RNA-Seq). Independently of the antibiotic pressure, most of the plasmid-backbone genes were expressed at low levels. The most expressed pBIC1a genes were involved in antibiotic resistance (blaKPC−2, blaTEM and aph(3′)-I), in plasmid replication and conjugation, or associated to mobile elements. After antibiotic exposure, 34% of E. coli (pBIC1a) genome was differentially expressed. Induction of oxidative stress response was evidenced, with numerous upregulated genes of the SoxRS/OxyR oxydative stress regulons, the Fur regulon (for iron uptake machinery), and IscR regulon (for iron sulfur cluster synthesis). Nine genes carried by pBIC1a were up-regulated, including the murein DD-endopeptidase mepM and the copper resistance operon. Despite the presence of a carbapenemase, we observed a major impact on E. coli (pBIC1a) whole transcriptome after imipenem exposure, but no effect on the level of transcription of antimicrobial resistance genes. We describe adaptive responses of E. coli to imipenem-induced stress, and identified plasmid-encoded genes that could be involved in resistance to stressful environments.

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A 4.5-Year Within-Patient Evolution of a Colistin-Resistant Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae Sequence Type 258

Abstract: Broad genomic and phenotypic diversification and the parallel selection of pathoadaptive mutations might contribute to long-term carriage and virulence of KPC-Kp CG258 strains and to the dissemination of this clone.

Cited by 46 publications

References 37 publications

Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years

Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years

First Description of Colistin and Tigecycline-Resistant Acinetobacter baumannii Producing KPC-3 Carbapenemase in Portugal

Transcriptional Landscape of a blaKPC-2 Plasmid and Response to Imipenem Exposure in Escherichia coli TOP10

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