Context-aware genomic surveillance reveals hidden transmission of a carbapenemase-producing Klebsiella pneumoniae

Author:

Viehweger Adrian1ORCID,Blumenscheit Christian2ORCID,Lippmann Norman1,Wyres Kelly L.3ORCID,Brandt Christian4ORCID,Hans Jörg B.5,Hölzer Martin6ORCID,Irber Luiz7ORCID,Gatermann Sören5,Lübbert Christoph8ORCID,Pletz Mathias W.4ORCID,Holt Kathryn E.93,König Brigitte1

Affiliation:

1. Institute of Medical Microbiology and Virology, University Hospital Leipzig, Leipzig, Germany

2. ZBS 6: Proteomics and Spectroscopy, Robert Koch Institute, Berlin, Germany

3. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia

4. Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany

5. National Reference Center for multidrug-resistant Gram-negative bacteria, Department for Medical Microbiology, Ruhr-University Bochum, Bochum, Germany

6. Methodology and Research Infrastructure, MF1 Bioinformatics, Robert Koch Institute, Berlin, Germany

7. Department of Population Health and Reproduction, University of California, Davis, Davis, California, USA

8. Division of Infectious Diseases and Tropical Medicine, Department of Medicine II, University Hospital Leipzig, Leipzig, Germany

9. Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK

Abstract

Genomic surveillance can inform effective public health responses to pathogen outbreaks. However, integration of non-local data is rarely done. We investigate two large hospital outbreaks of a carbapenemase-carrying Klebsiella pneumoniae strain in Germany and show the value of contextual data. By screening about 10 000 genomes, over 400 000 metagenomes and two culture collections using in silico and in vitro methods, we identify a total of 415 closely related genomes reported in 28 studies. We identify the relationship between the two outbreaks through time-dated phylogeny, including their respective origin. One of the outbreaks presents extensive hidden transmission, with descendant isolates only identified in other studies. We then leverage the genome collection from this meta-analysis to identify genes under positive selection. We thereby identify an inner membrane transporter (ynjC) with a putative role in colistin resistance. Contextual data from other sources can thus enhance local genomic surveillance at multiple levels and should be integrated by default when available.

Publisher

Microbiology Society

Subject

General Medicine

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