IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital

One of the most demanding challenges in infection control is the worldwide dissemination of multidrug-resistant (MDR) bacteria in clinical settings. Especially the increasing prevalence of carbapenemase producing Gram-negative pathogens poses an urgent threat to public health, as these enzymes confe...

Full description

Bibliographic Details
Main Authors: Robert E. Weber, Michael Pietsch, Andre Frühauf, Yvonne Pfeifer, Maria Martin, Dirk Luft, Sören Gatermann, Niels Pfennigwerth, Martin Kaase, Guido Werner, Stephan Fuchs
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-12-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2019.02817/full
id doaj-0f2fc295c8e743909bd74e88d7790836
record_format Article
spelling doaj-0f2fc295c8e743909bd74e88d77908362020-11-25T01:30:03ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-12-011010.3389/fmicb.2019.02817497458IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German HospitalRobert E. Weber0Michael Pietsch1Andre Frühauf2Yvonne Pfeifer3Maria Martin4Dirk Luft5Sören Gatermann6Niels Pfennigwerth7Martin Kaase8Guido Werner9Stephan Fuchs10Department of Infectious Diseases, Robert Koch-Institute, Wernigerode, GermanyDepartment of Infectious Diseases, Robert Koch-Institute, Wernigerode, GermanyDepartment of Infectious Diseases, Robert Koch-Institute, Wernigerode, GermanyDepartment of Infectious Diseases, Robert Koch-Institute, Wernigerode, GermanySLK-Kliniken Heilbronn, Institute for Infection Prevention and Clinical Hygiene, Heilbronn, GermanySLK-Kliniken Heilbronn, Institute for Infection Prevention and Clinical Hygiene, Heilbronn, GermanyGerman National Reference Centre for Multidrug-Resistant Gram-Negative Bacteria, Department of Medical Microbiology, Ruhr-University Bochum, Bochum, GermanyGerman National Reference Centre for Multidrug-Resistant Gram-Negative Bacteria, Department of Medical Microbiology, Ruhr-University Bochum, Bochum, GermanyGerman National Reference Centre for Multidrug-Resistant Gram-Negative Bacteria, Department of Medical Microbiology, Ruhr-University Bochum, Bochum, GermanyDepartment of Infectious Diseases, Robert Koch-Institute, Wernigerode, GermanyDepartment of Infectious Diseases, Robert Koch-Institute, Wernigerode, GermanyOne of the most demanding challenges in infection control is the worldwide dissemination of multidrug-resistant (MDR) bacteria in clinical settings. Especially the increasing prevalence of carbapenemase producing Gram-negative pathogens poses an urgent threat to public health, as these enzymes confer resistance to almost all β-lactam antibiotics including carbapenems. In this study, we report a prolonged nosocomial outbreak of various NDM-1-producing Enterobacterales species due to clonal spread and cross-species exchange of plasmids and possibly transposons. Between July 2015 and September 2017, a total of 51 carbapenemase-positive isolates were collected from 38 patients and three environmental sources in a single German hospital. Combining molecular typing methods and whole genome sequencing, the metallo-β-lactamase gene blaNDM–1 was found to be present in 35 isolates of which seven additionally carried the carbapenemase gene blaKPC–2. Core genome MLST (cgMLST) revealed different clusters of closely related isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Morganella morganii or Enterobacter cloacae indicating clonal spread. The detailed reconstruction of the plasmid sequences revealed that in all outbreak-associated isolates blaNDM–1 was located on similar composite transposons, which were also very similar to Tn125 previously described for Acinetobacter baumannii. In contrast to Tn125, these structures were flanked by IS26 elements, which could facilitate horizontal gene transfer. Moreover, the identical plasmid was found to be shared by E. coli and M. morganii isolates. Our results highlight the importance of detailed genome-based analyses for complex nosocomial outbreaks, allowing the identification of causal genetic determinants and providing insights into potential mechanisms involved in the dissemination of antibiotic resistances between different bacterial species.https://www.frontiersin.org/article/10.3389/fmicb.2019.02817/fullantibiotic resistancecarbapenemasehorizontal gene transferwhole genome sequencingNDM-1KPC-2
collection DOAJ
language English
format Article
sources DOAJ
author Robert E. Weber
Michael Pietsch
Andre Frühauf
Yvonne Pfeifer
Maria Martin
Dirk Luft
Sören Gatermann
Niels Pfennigwerth
Martin Kaase
Guido Werner
Stephan Fuchs
spellingShingle Robert E. Weber
Michael Pietsch
Andre Frühauf
Yvonne Pfeifer
Maria Martin
Dirk Luft
Sören Gatermann
Niels Pfennigwerth
Martin Kaase
Guido Werner
Stephan Fuchs
IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital
Frontiers in Microbiology
antibiotic resistance
carbapenemase
horizontal gene transfer
whole genome sequencing
NDM-1
KPC-2
author_facet Robert E. Weber
Michael Pietsch
Andre Frühauf
Yvonne Pfeifer
Maria Martin
Dirk Luft
Sören Gatermann
Niels Pfennigwerth
Martin Kaase
Guido Werner
Stephan Fuchs
author_sort Robert E. Weber
title IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital
title_short IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital
title_full IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital
title_fullStr IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital
title_full_unstemmed IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital
title_sort is26-mediated transfer of blandm–1 as the main route of resistance transmission during a polyclonal, multispecies outbreak in a german hospital
publisher Frontiers Media S.A.
series Frontiers in Microbiology
issn 1664-302X
publishDate 2019-12-01
description One of the most demanding challenges in infection control is the worldwide dissemination of multidrug-resistant (MDR) bacteria in clinical settings. Especially the increasing prevalence of carbapenemase producing Gram-negative pathogens poses an urgent threat to public health, as these enzymes confer resistance to almost all β-lactam antibiotics including carbapenems. In this study, we report a prolonged nosocomial outbreak of various NDM-1-producing Enterobacterales species due to clonal spread and cross-species exchange of plasmids and possibly transposons. Between July 2015 and September 2017, a total of 51 carbapenemase-positive isolates were collected from 38 patients and three environmental sources in a single German hospital. Combining molecular typing methods and whole genome sequencing, the metallo-β-lactamase gene blaNDM–1 was found to be present in 35 isolates of which seven additionally carried the carbapenemase gene blaKPC–2. Core genome MLST (cgMLST) revealed different clusters of closely related isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Morganella morganii or Enterobacter cloacae indicating clonal spread. The detailed reconstruction of the plasmid sequences revealed that in all outbreak-associated isolates blaNDM–1 was located on similar composite transposons, which were also very similar to Tn125 previously described for Acinetobacter baumannii. In contrast to Tn125, these structures were flanked by IS26 elements, which could facilitate horizontal gene transfer. Moreover, the identical plasmid was found to be shared by E. coli and M. morganii isolates. Our results highlight the importance of detailed genome-based analyses for complex nosocomial outbreaks, allowing the identification of causal genetic determinants and providing insights into potential mechanisms involved in the dissemination of antibiotic resistances between different bacterial species.
topic antibiotic resistance
carbapenemase
horizontal gene transfer
whole genome sequencing
NDM-1
KPC-2
url https://www.frontiersin.org/article/10.3389/fmicb.2019.02817/full
work_keys_str_mv AT roberteweber is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT michaelpietsch is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT andrefruhauf is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT yvonnepfeifer is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT mariamartin is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT dirkluft is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT sorengatermann is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT nielspfennigwerth is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT martinkaase is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT guidowerner is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
AT stephanfuchs is26mediatedtransferofblandm1asthemainrouteofresistancetransmissionduringapolyclonalmultispeciesoutbreakinagermanhospital
_version_ 1725093926436601856