Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains

Lucy van Dorp (Corresponding Author), Qi Wang, Liam P. Shaw, Mislav Acman, Ola B. Brynildsrud, Vegard Eldholm, Ruobing Wang, Hua Gao, Yuyao Yin, Hongbin Chen, Chuling Ding, Rhys A. Farrer, Xavier Didelot, Francois Balloux (Corresponding Author), Hui Wang (Corresponding Author)

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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 bla KPC-2-positive CRKP infection, close monitoring was put in place over the course of 14 months to characterize all bla KPC-2-positive CRKP in circulation in the hospital. Whole genome sequences were generated for 100 isolates from bla KPC-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 bla KPC-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.
Original languageEnglish
Number of pages11
JournalMicrobial Genomics
Early online date2 Apr 2019
Publication statusPublished - 2019

Bibliographical note

L. v. D., L. P. S., X. D., H. W. and F. B. acknowledge financial support from the Newton Trust UK–China NSFC initiative (grants MR/P007597/1 and 81661138006). F. B. acknowledges support from the BBSRC GCRF scheme. H. W. additionally acknowledges support from China NSFC grant 81625014. H. C. acknowledges financial support from a 111 Talent Discipline Planning of PKUPH award for a 1-year visit at University College London.

Data statement: All supporting data, code and protocols have been provided within the article or through supplementary data files. Nine supplementary tables and fifteen supplementary figures are available with the online version of this article.


  • nosocomial pathogens
  • antimicrobial resistance
  • carbapenem-resistant Klebsiella pneumoniae (CRKP)
  • horizontal gene transfer
  • plasmids
  • transmission chains
  • ST11
  • KPC
  • Plasmids
  • Transmission chains
  • Nosocomial pathogens
  • Carbapenem-resistant Klebsiella pneumoniae (CRKP)
  • Antimicrobial resistance
  • Horizontal gene transfer


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