Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type 147 Recovered from Germany

Kyriaki Xanthopoulou; Alessandra Carattoli; Julia Wille; Lena M Biehl; Holger Rohde; Fedja Farowski; Oleg Krut; Laura Villa; Claudia Feudi; Harald Seifert; Paul G Higgins

doi:10.3390/antibiotics9100675

Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type 147 Recovered from Germany

Antibiotics (Basel). 2020 Oct 5;9(10):675. doi: 10.3390/antibiotics9100675.

Authors

Kyriaki Xanthopoulou^{1

2}, Alessandra Carattoli³, Julia Wille^{1

2}, Lena M Biehl^{2

4}, Holger Rohde^{5

6}, Fedja Farowski^{2

4

7}, Oleg Krut⁸, Laura Villa⁹, Claudia Feudi¹⁰, Harald Seifert^{1

2}, Paul G Higgins^{1

2}

Affiliations

¹ Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany.
² German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, 50935 Cologne, Germany.
³ Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy.
⁴ Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany.
⁵ Institute for Medical Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany.
⁶ German Centre for Infection Research, Partner site Hamburg-Lübeck-Borstel, 20246 Hamburg, Germany.
⁷ Department of Internal Medicine II, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
⁸ Paul-Ehrlich Institute, Federal Institute for Vaccines and Biomedicine, 63225 Langen, Germany.
⁹ Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
¹⁰ Institute of Microbiology and Epizootics, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany.

Abstract

Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the bla_OXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare.

Keywords: carbapenem resistance, carbapenemase, whole genome sequencing, long reads, plasmid, Klebsiella pneumoniae, extensively drug-resistant, molecular typing.