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    Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing

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    Author
    Mu, A; Kwong, JC; Isles, NS; da Silva, AG; Schultz, MB; Ballard, SA; Lane, CR; Carter, GP; Williamson, DA; Seemann, T; ...
    Date
    2019-01-01
    Source Title
    mSphere
    Publisher
    AMER SOC MICROBIOLOGY
    University of Melbourne Author/s
    Seemann, Torsten; Howden, Benjamin; Schultz, Mark; Lane, Courtney; Kwong, Jason; Goncalves Da Silva, Anders; Stinear, Timothy; Mu, Andre; Carter, Glen; Batt, Susan; ...
    Affiliation
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Mu, A., Kwong, J. C., Isles, N. S., da Silva, A. G., Schultz, M. B., Ballard, S. A., Lane, C. R., Carter, G. P., Williamson, D. A., Seemann, T., Stinear, T. P. & Howden, B. P. (2019). Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing. MSPHERE, 4 (1), https://doi.org/10.1128/mSphere.00529-18.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253526
    DOI
    10.1128/mSphere.00529-18
    Abstract
    Culture-independent methods that target genome fragments have shown promise in identifying certain pathogens, but the holy grail of comprehensive pathogen genome detection from microbiologically complex samples for subsequent forensic analyses remains a challenge. In the context of an investigation of a nosocomial outbreak, we used shotgun metagenomic sequencing of a human fecal sample and a neural network algorithm based on tetranucleotide frequency profiling to reconstruct microbial genomes and tested the same approach using rectal swabs from a second patient. The approach rapidly and readily detected the genome of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in the patient fecal specimen and in the rectal swab sample, achieving a level of strain resolution that was sufficient for confident transmission inference during a highly clonal outbreak. The analysis also detected previously unrecognized colonization of the patient by vancomycin-resistant Enterococcus faecium, another multidrug-resistant bacterium.IMPORTANCE The study results reported here perfectly demonstrate the power and promise of clinical metagenomics to recover genome sequences of important drug-resistant bacteria and to rapidly provide rich data that inform outbreak investigations and treatment decisions, independently of the need to culture the organisms.

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