PUBLICATION

Adaptive evolution of virulence and persistence in carbapenem-resistant Klebsiella pneumoniae

Authors
Ernst, C.M., Braxton, J.R., Rodriguez-Osorio, C.A., Zagieboylo, A.P., Li, L., Pironti, A., Manson, A.L., Nair, A.V., Benson, M., Cummins, K., Clatworthy, A.E., Earl, A.M., Cosimi, L.A., Hung, D.T.
ID
ZDB-PUB-200825-17
Date
2020
Source
Nature medicine   26: 705-711 (Journal)
Registered Authors
Clatworthy, Anne, Hung, Deborah
Keywords
none
MeSH Terms
  • Adaptation, Biological/genetics*
  • Adult
  • Animals
  • Bacterial Capsules/genetics
  • Carbapenem-Resistant Enterobacteriaceae/classification
  • Carbapenem-Resistant Enterobacteriaceae/genetics*
  • Carbapenem-Resistant Enterobacteriaceae/isolation & purification
  • Carbapenem-Resistant Enterobacteriaceae/pathogenicity
  • Carbapenems/therapeutic use
  • Cells, Cultured
  • Evolution, Molecular*
  • Female
  • Genome, Bacterial
  • Humans
  • Klebsiella Infections/microbiology
  • Klebsiella Infections/urine
  • Klebsiella pneumoniae/classification
  • Klebsiella pneumoniae/genetics*
  • Klebsiella pneumoniae/isolation & purification
  • Klebsiella pneumoniae/pathogenicity
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Transgenic
  • Phylogeny
  • Polymorphism, Single Nucleotide
  • Urinary Tract Infections/microbiology
  • Urinary Tract Infections/urine
  • Virulence/genetics*
  • Zebrafish
  • beta-Lactam Resistance/genetics*
PubMed
32284589 Full text @ Nat. Med.
Abstract
Among the most urgent public health threats is the worldwide emergence of carbapenem-resistant Enterobacteriaceae1-4, which are resistant to the antibiotic class of 'last resort'. In the United States and Europe, carbapenem-resistant strains of the Klebsiella pneumoniae ST258 (ref. 5) sequence type are dominant, endemic6-8 and associated with high mortality6,9,10. We report the global evolution of pathogenicity in carbapenem-resistant K. pneumoniae, resulting in the repeated convergence of virulence and carbapenem resistance in the United States and Europe, dating back to as early as 2009. We demonstrate that K. pneumoniae can enhance its pathogenicity by adopting two opposing infection programs through easily acquired gain- and loss-of-function mutations. Single-nucleotide polymorphisms in the capsule biosynthesis gene wzc lead to hypercapsule production, which confers phagocytosis resistance, enhanced dissemination and increased mortality in animal models. In contrast, mutations disrupting capsule biosynthesis genes impair capsule production, which enhances epithelial cell invasion, in vitro biofilm formation and persistence in urinary tract infections. These two types of capsule mutants have emerged repeatedly and independently in Europe and the United States, with hypercapsule mutants associated with bloodstream infections and capsule-deficient mutants associated with urinary tract infections. In the latter case, drug-tolerant K. pneumoniae can persist to yield potentially untreatable, persistent infection.
Errata / Notes
This article is corrected by ZDB-PUB-220906-208.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping