Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31990-1
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Funding
- Bioinformatics Core of the University of Michigan Medical School's Biomedical Research Core Facilities
- National Institution of Health [R01AI125307, 1R01AI14825901]
- Postdoctoral Translational Scholar Program [NIH UL1TR002240]
- University of Michigan bioinformatics training grant [NIH T32GM070449]
- Molecular Mechanisms in Microbial Pathogenesis Training Program [T32 AI007528]
- Lung Immunopathology Training Program [T32HL007517]
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This study identifies several genes reproducibly associated with progression to infection in patients colonized by diverse Klebsiella. Patient variables, such as comorbidities, partially explain which patients will progress to Klebsiella infection, with colonization of the gut acting as a reservoir. Little is known, however, regarding Klebsiella genes that may increase risk of disease in colonized individuals.
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. Patient variables, such as comorbidities, partially explain which patients will progress to Klebsiella infection, with colonization of the gut acting as a reservoir. Little is known, however, regarding Klebsiella genes that may increase risk of disease in colonized individuals. Here, authors conduct a comparative genomics study to identify genes associated with progression from colonisation to infection.
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