Dorp, Lucy van, Wang, Qi, Shaw, Liam P., Acman, Mislav, Brynildsrud, Ola B., Eldholm, Vegard, Wang, Ruobing, Gao, Hua, Yin, Yuyao, Chen, Hongbin, Ding, Chuling, Farrer, Rhys A., Didelot, Xavier, Balloux, Francois and Wang, Hui (2019) Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains. Microbial Genomics, 5 (4). doi:10.1099/mgen.0.000263 ISSN 2057-5858.

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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 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.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Klebsiella pneumoniae, Multidrug resistance
Journal or Publication Title:	Microbial Genomics
Publisher:	Microbiology Society
ISSN:	2057-5858
Official Date:	2 April 2019
Dates:	Date Event 2 April 2019 Published 11 March 2019 Accepted
Volume:	5
Number:	4
Number of Pages:	9
DOI:	10.1099/mgen.0.000263
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	4 April 2019
Date of first compliant Open Access:	4 April 2019
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID MR/P007597/1 Isaac Newton Trust http://dx.doi.org/10.13039/501100004815 MR/P007597/1 [NSFC] National Natural Science Foundation of China http://dx.doi.org/10.13039/501100001809 81661138006 Isaac Newton Trust http://dx.doi.org/10.13039/501100004815 81661138006 [NSFC] National Natural Science Foundation of China http://dx.doi.org/10.13039/501100001809 UNSPECIFIED [BBSRC] Biotechnology and Biological Sciences Research Council http://dx.doi.org/10.13039/501100000268 UNSPECIFIED Global Challenges Research Fund UNSPECIFIED 81625014 [NSFC] National Natural Science Foundation of China http://dx.doi.org/10.13039/501100001809 111 Talents Plan [MEPRC] Ministry of Education of the People's Republic of China http://dx.doi.org/10.13039/501100002338

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