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Combined comparative genomics and clinical modeling reveals plasmid-encoded genes are independently associated with Klebsiella infection

Author

Listed:
  • Jay Vornhagen

    (University of Michigan
    University of Michigan)

  • Emily K. Roberts

    (University of Michigan)

  • Lavinia Unverdorben

    (University of Michigan)

  • Sophia Mason

    (University of Michigan)

  • Alieysa Patel

    (University of Michigan)

  • Ryan Crawford

    (University of Michigan)

  • Caitlyn L. Holmes

    (University of Michigan
    University of Michigan)

  • Yuang Sun

    (University of Michigan)

  • Alexandra Teodorescu

    (University of Michigan)

  • Evan S. Snitkin

    (University of Michigan
    University of Michigan)

  • Lili Zhao

    (University of Michigan)

  • Patricia J. Simner

    (Johns Hopkins University School of Medicine)

  • Pranita D. Tamma

    (Johns Hopkins University School of Medicine)

  • Krishna Rao

    (University of Michigan)

  • Keith S. Kaye

    (University of Michigan)

  • Michael A. Bachman

    (University of Michigan
    University of Michigan)

Abstract

Members of the Klebsiella pneumoniae species complex frequently colonize the gut and colonization is associated with subsequent infection. To identify genes associated with progression from colonization to infection, we undertook a case-control comparative genomics study. Concordant cases (N = 85), where colonizing and invasive isolates were identical strain types, were matched to asymptomatically colonizing controls (N = 160). Thirty-seven genes are associated with infection, 27 of which remain significant following adjustment for patient variables and bacterial phylogeny. Infection-associated genes are not previously characterized virulence factors, but instead a diverse group of stress resistance, regulatory and antibiotic resistance genes, despite careful adjustment for antibiotic exposure. Many genes are plasmid borne, and for some, the relationship with infection is mediated by gut dominance. Five genes were validated in a geographically-independent cohort of colonized patients. This study identifies several genes reproducibly associated with progression to infection in patients colonized by diverse Klebsiella.

Suggested Citation

  • Jay Vornhagen & Emily K. Roberts & Lavinia Unverdorben & Sophia Mason & Alieysa Patel & Ryan Crawford & Caitlyn L. Holmes & Yuang Sun & Alexandra Teodorescu & Evan S. Snitkin & Lili Zhao & Patricia J., 2022. "Combined comparative genomics and clinical modeling reveals plasmid-encoded genes are independently associated with Klebsiella infection," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31990-1
    DOI: 10.1038/s41467-022-31990-1
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    References listed on IDEAS

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    2. Bates, Douglas & Mächler, Martin & Bolker, Ben & Walker, Steve, 2015. "Fitting Linear Mixed-Effects Models Using lme4," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 67(i01).
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    4. Leonardos Mageiros & Guillaume Méric & Sion C. Bayliss & Johan Pensar & Ben Pascoe & Evangelos Mourkas & Jessica K. Calland & Koji Yahara & Susan Murray & Thomas S. Wilkinson & Lisa K. Williams & Matt, 2021. "Author Correction: Genome evolution and the emergence of pathogenicity in avian Escherichia coli," Nature Communications, Nature, vol. 12(1), pages 1-2, December.
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