Cargando…

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

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 appear...

Descripción completa

Detalles Bibliográficos
Autores principales: Heiden, Stefan E., Hübner, Nils-Olaf, Bohnert, Jürgen A., Heidecke, Claus-Dieter, Kramer, Axel, Balau, Veronika, Gierer, Wolfgang, Schaefer, Stephan, Eckmanns, Tim, Gatermann, Sören, Eger, Elias, Guenther, Sebastian, Becker, Karsten, Schaufler, Katharina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724794/
https://www.ncbi.nlm.nih.gov/pubmed/33298160
http://dx.doi.org/10.1186/s13073-020-00814-6
_version_ 1783620590415904768
author Heiden, Stefan E.
Hübner, Nils-Olaf
Bohnert, Jürgen A.
Heidecke, Claus-Dieter
Kramer, Axel
Balau, Veronika
Gierer, Wolfgang
Schaefer, Stephan
Eckmanns, Tim
Gatermann, Sören
Eger, Elias
Guenther, Sebastian
Becker, Karsten
Schaufler, Katharina
author_facet Heiden, Stefan E.
Hübner, Nils-Olaf
Bohnert, Jürgen A.
Heidecke, Claus-Dieter
Kramer, Axel
Balau, Veronika
Gierer, Wolfgang
Schaefer, Stephan
Eckmanns, Tim
Gatermann, Sören
Eger, Elias
Guenther, Sebastian
Becker, Karsten
Schaufler, Katharina
author_sort Heiden, Stefan E.
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-020-00814-6.
format Online
Article
Text
id pubmed-7724794
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-77247942020-12-09 A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition Heiden, Stefan E. Hübner, Nils-Olaf Bohnert, Jürgen A. Heidecke, Claus-Dieter Kramer, Axel Balau, Veronika Gierer, Wolfgang Schaefer, Stephan Eckmanns, Tim Gatermann, Sören Eger, Elias Guenther, Sebastian Becker, Karsten Schaufler, Katharina Genome Med Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-020-00814-6. BioMed Central 2020-12-09 /pmc/articles/PMC7724794/ /pubmed/33298160 http://dx.doi.org/10.1186/s13073-020-00814-6 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Heiden, Stefan E.
Hübner, Nils-Olaf
Bohnert, Jürgen A.
Heidecke, Claus-Dieter
Kramer, Axel
Balau, Veronika
Gierer, Wolfgang
Schaefer, Stephan
Eckmanns, Tim
Gatermann, Sören
Eger, Elias
Guenther, Sebastian
Becker, Karsten
Schaufler, Katharina
A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
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 Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724794/
https://www.ncbi.nlm.nih.gov/pubmed/33298160
http://dx.doi.org/10.1186/s13073-020-00814-6
work_keys_str_mv AT heidenstefane aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT hubnernilsolaf aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT bohnertjurgena aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT heideckeclausdieter aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT krameraxel aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT balauveronika aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT giererwolfgang aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT schaeferstephan aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT eckmannstim aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT gatermannsoren aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT egerelias aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT guenthersebastian aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT beckerkarsten aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT schauflerkatharina aklebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT heidenstefane klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT hubnernilsolaf klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT bohnertjurgena klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT heideckeclausdieter klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT krameraxel klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT balauveronika klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT giererwolfgang klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT schaeferstephan klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT eckmannstim klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT gatermannsoren klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT egerelias klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT guenthersebastian klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT beckerkarsten klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition
AT schauflerkatharina klebsiellapneumoniaest307outbreakclonefromgermanydemonstratesfeaturesofextensivedrugresistancehypermucoviscosityandenhancedironacquisition