TY - JOUR
T1 - Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae
AU - The European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) Working Group
AU - The ESCMID Study Group for Epidemiological Markers (ESGEM)
AU - David, Sophia
AU - Cohen, Victoria
AU - Reuter, Sandra
AU - Sheppard, Anna E.
AU - Giani, Tommaso
AU - Parkhill, Julian
AU - Rossolini, Gian Maria
AU - Feil, Edward J.
AU - Grundmann, Hajo
AU - Aanensen, David M.
AU - Koraqi, Andi
AU - Lacej, Denada
AU - Apfalter, Petra
AU - Hartl, Rainer
AU - Glupczynski, Youri
AU - Huang, Te Din
AU - Strateva, Tanya
AU - Marteva-Proevska, Yuliya
AU - Andrasevic, Arjana Tambic
AU - Butic, Iva
AU - Pieridou-Bagatzouni, Despo
AU - Maikanti-Charalampous, Panagiota
AU - Hrabak, Jaroslav
AU - Zemlickova, Helena
AU - Hammerum, Anette
AU - Jakobsen, Lotte
AU - Ivanova, Marina
AU - Pavelkovich, Anastasia
AU - Jalava, Jari
AU - Osterblad, Monica
AU - Dortet, Laurent
AU - Vaux, Sophie
AU - Kaase, Martin
AU - Gatermann, Soren G.
AU - Vatopoulos, Alkiviadis
AU - Tryfinopoulou, Kyriaki
AU - Toth, Akos
AU - Janvari, Laura
AU - Boo, Teck Wee
AU - McGrath, Elaine
AU - Carmeli, Yehuda
AU - Adler, Amos
AU - Pantosti, Annalisa
AU - Monaco, Monica
AU - Raka, Lul
AU - Kurti, Arsim
AU - Balode, Arta
AU - Saule, Mara
AU - Woodford, Neil
AU - Hopkins, Katie
N1 - Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/10/6
Y1 - 2020/10/6
N2 - Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with lowresolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, blaOXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, blaVIM and blaNDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, blaKPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying blaKPC. Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread.
AB - Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with lowresolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, blaOXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, blaVIM and blaNDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, blaKPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying blaKPC. Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread.
KW - Carbapenem resistance
KW - Carbapenemase genes
KW - Genomics
KW - Klebsiella pneumoniae
KW - Plasmids
UR - http://www.scopus.com/inward/record.url?scp=85092682175&partnerID=8YFLogxK
U2 - 10.1073/pnas.2003407117
DO - 10.1073/pnas.2003407117
M3 - Article
C2 - 32968015
AN - SCOPUS:85092682175
SN - 0027-8424
VL - 117
SP - 25043
EP - 25054
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 40
ER -