Age-Dependent Susceptibility to Enteropathogenic Escherichia coli (EPEC) Infection in Mice

PLoS Pathog. 2016 May 9;12(5):e1005616. doi: 10.1371/journal.ppat.1005616. eCollection 2016 May.


Enteropathogenic Escherichia coli (EPEC) represents a major causative agent of infant diarrhea associated with significant morbidity and mortality in developing countries. Although studied extensively in vitro, the investigation of the host-pathogen interaction in vivo has been hampered by the lack of a suitable small animal model. Using RT-PCR and global transcriptome analysis, high throughput 16S rDNA sequencing as well as immunofluorescence and electron microscopy, we characterize the EPEC-host interaction following oral challenge of newborn mice. Spontaneous colonization of the small intestine and colon of neonate mice that lasted until weaning was observed. Intimate attachment to the epithelial plasma membrane and microcolony formation were visualized only in the presence of a functional bundle forming pili (BFP) and type III secretion system (T3SS). Similarly, a T3SS-dependent EPEC-induced innate immune response, mediated via MyD88, TLR5 and TLR9 led to the induction of a distinct set of genes in infected intestinal epithelial cells. Infection-induced alterations of the microbiota composition remained restricted to the postnatal period. Although EPEC colonized the adult intestine in the absence of a competing microbiota, no microcolonies were observed at the small intestinal epithelium. Here, we introduce the first suitable mouse infection model and describe an age-dependent, virulence factor-dependent attachment of EPEC to enterocytes in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal*
  • Disease Susceptibility / microbiology
  • Enteropathogenic Escherichia coli / metabolism
  • Enteropathogenic Escherichia coli / pathogenicity*
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / microbiology*
  • Fimbriae, Bacterial / ultrastructure
  • Fluorescent Antibody Technique
  • Host-Pathogen Interactions / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron
  • Oligonucleotide Array Sequence Analysis
  • Type III Secretion Systems / metabolism
  • Virulence Factors / metabolism


  • Type III Secretion Systems
  • Virulence Factors

Grants and funding

This work was supported by: Deutsche Forschungsgemeinschaft Ho2236/8-1 to MWH, Deutsche Forschungsgemeinschaft SFB900 (A4) to MWH, Deutsche Forschungsgemeinschaft Priority Program 1656 to MWH, Deutsche Forschungsgemeinschaft Priority Program 1580 to UR and MWH, State of Lower Saxony Lower Saxony-Israel Collaboration Research Found to IR and MWH, State of Lower Saxony N-RENNT to MWH, and Deutsche Forschungsgemeinschaft HBRS to KZ. MF received support by the Freie Universität Berlin within the Excellence Initiative of the German Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.