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

• Published in: PLoS pathogens Vol. 12; no. 5; p. e1005616
• Main Authors: Dupont, Aline, Sommer, Felix, Zhang, Kaiyi, Repnik, Urska, Basic, Marijana, Bleich, André, Kühnel, Mark, Bäckhed, Fredrik, Litvak, Yael, Fulde, Marcus, Rosenshine, Ilan, Hornef, Mathias W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2016; Public Library of Science (PLoS)
• Subjects: Age; Analysis; Animals; Animals, Newborn; attachment; barrier function; Biology and Life Sciences; bundle-forming pilus; children; Clinical Medicine; Developing countries; diarrhea; Disease Models, Animal; Disease Susceptibility - microbiology; E coli; Enteropathogenic Escherichia coli - metabolism; Enteropathogenic Escherichia coli - pathogenicity; Escherichia coli; Escherichia coli Infections - metabolism; Escherichia coli Infections - microbiology; Fimbriae, Bacterial - ultrastructure; Fluorescent Antibody Technique; Genetic aspects; host; Host-Pathogen Interactions - physiology; Infections; intestinal epithelial-cells; intimate adherence; Klinisk medicin; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Microscopy, Electron; Morbidity; Mortality; mouse model; Oligonucleotide Array Sequence Analysis; Parasitology; Pathogens; Research and Analysis Methods; Rodents; Small intestine; Studies; Type III Secretion Systems - metabolism; Virology; Virulence Factors - metabolism
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1005616

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.