A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition

Abstract Background Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage ha...

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Main Authors: Stefan E. Heiden, Nils-Olaf Hübner, Jürgen A. Bohnert, Claus-Dieter Heidecke, Axel Kramer, Veronika Balau, Wolfgang Gierer, Stephan Schaefer, Tim Eckmanns, Sören Gatermann, Elias Eger, Sebastian Guenther, Karsten Becker, Katharina Schaufler
Format: Article
Language:English
Published: BMC 2020-12-01
Series:Genome Medicine
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Online Access:https://doi.org/10.1186/s13073-020-00814-6
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author Stefan E. Heiden
Nils-Olaf Hübner
Jürgen A. Bohnert
Claus-Dieter Heidecke
Axel Kramer
Veronika Balau
Wolfgang Gierer
Stephan Schaefer
Tim Eckmanns
Sören Gatermann
Elias Eger
Sebastian Guenther
Karsten Becker
Katharina Schaufler
author_facet Stefan E. Heiden
Nils-Olaf Hübner
Jürgen A. Bohnert
Claus-Dieter Heidecke
Axel Kramer
Veronika Balau
Wolfgang Gierer
Stephan Schaefer
Tim Eckmanns
Sören Gatermann
Elias Eger
Sebastian Guenther
Karsten Becker
Katharina Schaufler
author_sort Stefan E. Heiden
collection DOAJ
description Abstract Background Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany. Methods Here, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone. Results Phylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, which K. pneumoniae ST307 likely donated to other K. pneumoniae isolates of different STs and even other bacterial species (e.g., Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulent K. pneumoniae strain (hvKP1). Conclusions The combination of extensive drug resistance and virulence, partly conferred through a “mosaic” plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.
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spelling doaj.art-8e481b0612b54ca6b9da3ff8fc5d01332022-12-21T19:54:43ZengBMCGenome Medicine1756-994X2020-12-0112111510.1186/s13073-020-00814-6A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisitionStefan E. Heiden0Nils-Olaf Hübner1Jürgen A. Bohnert2Claus-Dieter Heidecke3Axel Kramer4Veronika Balau5Wolfgang Gierer6Stephan Schaefer7Tim Eckmanns8Sören Gatermann9Elias Eger10Sebastian Guenther11Karsten Becker12Katharina Schaufler13Institute of Pharmacy, Pharmaceutical Microbiology, University of GreifswaldCentral Unit for Infection Prevention and Control, University Medicine GreifswaldFriedrich Loeffler-Institute of Medical Microbiology, University Medicine GreifswaldDepartment of General, Visceral, Thoracic and Vascular Surgery, University Medicine GreifswaldInstitute for Hygiene and Environmental Medicine, University Medicine GreifswaldIMD Laboratory Greifswald, Institute of Medical DiagnosticsMVZ Laboratory Limbach Vorpommern-RügenMVZ Laboratory Limbach Vorpommern-RügenDepartment for Infectious Disease Epidemiology, Robert Koch-InstituteNational Reference Centre for Multidrug-Resistant Gram-Negative Bacteria, Ruhr University BochumInstitute of Pharmacy, Pharmaceutical Microbiology, University of GreifswaldInstitute of Pharmacy, Pharmaceutical Biology, University of GreifswaldFriedrich Loeffler-Institute of Medical Microbiology, University Medicine GreifswaldInstitute of Pharmacy, Pharmaceutical Microbiology, University of GreifswaldAbstract Background Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany. Methods Here, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone. Results Phylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, which K. pneumoniae ST307 likely donated to other K. pneumoniae isolates of different STs and even other bacterial species (e.g., Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulent K. pneumoniae strain (hvKP1). Conclusions The combination of extensive drug resistance and virulence, partly conferred through a “mosaic” plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.https://doi.org/10.1186/s13073-020-00814-6XDR Klebsiella pneumoniaeOutbreakHypervirulencePlasmid transmission“Mosaic” plasmid
spellingShingle Stefan E. Heiden
Nils-Olaf Hübner
Jürgen A. Bohnert
Claus-Dieter Heidecke
Axel Kramer
Veronika Balau
Wolfgang Gierer
Stephan Schaefer
Tim Eckmanns
Sören Gatermann
Elias Eger
Sebastian Guenther
Karsten Becker
Katharina Schaufler
A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
Genome Medicine
XDR Klebsiella pneumoniae
Outbreak
Hypervirulence
Plasmid transmission
“Mosaic” plasmid
title A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
title_full A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
title_fullStr A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
title_full_unstemmed A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
title_short A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
title_sort klebsiella pneumoniae st307 outbreak clone from germany demonstrates features of extensive drug resistance hypermucoviscosity and enhanced iron acquisition
topic XDR Klebsiella pneumoniae
Outbreak
Hypervirulence
Plasmid transmission
“Mosaic” plasmid
url https://doi.org/10.1186/s13073-020-00814-6
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