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

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. Simner, Pranita D. Tamma, Krishna Rao, Keith S. Kaye and Michael A. Bachman ()
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Jay Vornhagen: 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
Yuang Sun: University of Michigan
Alexandra Teodorescu: University of Michigan
Evan S. Snitkin: 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

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31990-1

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