Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains
dc.contributor.author | van Dorp, L | |
dc.contributor.author | Wang, Q | |
dc.contributor.author | Shaw, LP | |
dc.contributor.author | Acman, M | |
dc.contributor.author | Brynildsrud, OB | |
dc.contributor.author | Eldholm, V | |
dc.contributor.author | Wang, R | |
dc.contributor.author | Gao, H | |
dc.contributor.author | Yin, Y | |
dc.contributor.author | Chen, H | |
dc.contributor.author | Ding, C | |
dc.contributor.author | Farrer, RA | |
dc.contributor.author | Didelot, X | |
dc.contributor.author | Balloux, F | |
dc.contributor.author | Wang, H | |
dc.date.accessioned | 2019-09-25T10:31:03Z | |
dc.date.issued | 2019-04-01 | |
dc.description.abstract | Carbapenem-resistant Klebsiella pneumoniae (CRKP) increasingly cause high-mortality outbreaks in hospital settings globally. Following a patient fatality at a hospital in Beijing due to a blaKPC-2-positive CRKP infection, close monitoring was put in place over the course of 14 months to characterize all blaKPC-2-positive CRKP in circulation in the hospital. Whole genome sequences were generated for 100 isolates from blaKPC-2-positive isolates from infected patients, carriers and the hospital environment. Phylogenetic analyses identified a closely related cluster of 82 sequence type 11 (ST11) isolates circulating in the hospital for at least a year prior to admission of the index patient. The majority of inferred transmissions for these isolates involved patients in intensive care units. Whilst the 82 ST11 isolates collected during the surveillance effort all had closely related chromosomes, we observed extensive diversity in their antimicrobial resistance (AMR) phenotypes. We were able to reconstruct the major genomic changes underpinning this variation in AMR profiles, including multiple gains and losses of entire plasmids and recombination events between plasmids, including transposition of blaKPC-2. We also identified specific cases where variation in plasmid copy number correlated with the level of phenotypic resistance to drugs, suggesting that the number of resistance elements carried by a strain may play a role in determining the level of AMR. Our findings highlight the epidemiological value of whole genome sequencing for investigating multi-drug-resistant hospital infections and illustrate that standard typing schemes cannot capture the extraordinarily fast genome evolution of CRKP isolates. | en_GB |
dc.description.sponsorship | Newton Trust UK–China NSFC initiative | en_GB |
dc.description.sponsorship | Newton Trust UK–China NSFC initiative | en_GB |
dc.description.sponsorship | China NSFC | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.identifier.citation | Vol. 5 (4) | en_GB |
dc.identifier.doi | 10.1099/mgen.0.000263 | |
dc.identifier.grantnumber | MR/P007597/1 | en_GB |
dc.identifier.grantnumber | 81661138006 | en_GB |
dc.identifier.grantnumber | 81625014 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/38879 | |
dc.language.iso | en | en_GB |
dc.publisher | Microbiology Society | en_GB |
dc.rights | © 2019 The Authors. This is an Open Access article published by the Microbiology Society under the Creative Commons Attribution License | en_GB |
dc.subject | antimicrobial resistance | en_GB |
dc.subject | carbapenem-resistant Klebsiella pneumoniae (CRKP) | en_GB |
dc.subject | horizontal gene transfer | en_GB |
dc.subject | nosocomial pathogens | en_GB |
dc.subject | plasmids | en_GB |
dc.subject | transmission chains | en_GB |
dc.title | Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-09-25T10:31:03Z | |
dc.identifier.issn | 2057-5858 | |
exeter.article-number | ARTN 000263 | en_GB |
dc.description | This is the final version. Available from the Microbiology Society via the DOI in this record. | en_GB |
dc.description | Raw Illumina short-read and PacBio long-read sequences have been deposited on NCBI with BioProject ID PRJNA508760. Full accompanying metadata and phenotypic resistance characterization are available in Tables S1 and S2 (available in the online version of this article). All programs used in bioinformatics analyses are publicly available. | en_GB |
dc.identifier.journal | Microbial Genomics | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-03-11 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-03-11 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-09-25T10:25:20Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-09-25T10:31:08Z | |
refterms.panel | A | en_GB |
refterms.depositException | publishedGoldOA |
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Except where otherwise noted, this item's licence is described as © 2019 The Authors. This is an Open Access article published by the Microbiology Society under the Creative Commons Attribution License