Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo: role of mitochondrial associated protein (Map)

Cell Microbiol. 2006 Oct;8(10):1669-86. doi: 10.1111/j.1462-5822.2006.00741.x. Epub 2006 Jun 7.


Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli are non-invasive attaching/effacing (A/E) bacterial pathogens that infect their host's intestinal epithelium, causing severe diarrhoeal disease. These bacteria utilize a type III secretion apparatus to deliver effector molecules into host cells, subverting cellular function. Mitochondrial associated protein (Map) is a multifunctional effector protein that targets host cell mitochondria and contributes to infection-induced epithelial barrier dysfunction in vitro. Unfortunately, the relevance of these actions to the pathogenesis of EPEC-induced disease is uncertain. Using Citrobacter rodentium, a mouse-adapted A/E bacterium, we found that Map colocalized with host cell mitochondria, and that in vivo infection led to a disruption of mitochondrial morphology in infected colonocytes as assessed by electron microscopy. Histochemical staining for the mitochondrial enzyme succinate dehydrogenase also revealed a significant loss of mitochondrial respiratory function in the infected intestinal epithelium; however, both pathologies were attenuated in mice infected with a Deltamap strain. C. rodentium Map was also implicated in the disruption of epithelial barrier function both in vitro and in vivo. These studies thus advance our understanding of how A/E pathogens subvert host cell functions and cause disease, demonstrating that Map contributes to the functional disruption of the intestinal epithelium during enteric infection by C. rodentium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / physiology*
  • Cell Line, Tumor
  • Citrobacter rodentium / pathogenicity
  • Citrobacter rodentium / physiology*
  • Colon / microbiology
  • Colon / pathology
  • Colony Count, Microbial
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / pathology*
  • Enterobacteriaceae Infections / physiopathology
  • Gene Deletion
  • HeLa Cells
  • Humans
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology*
  • Membrane Potentials
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / enzymology
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Membranes
  • Succinate Dehydrogenase / metabolism


  • Bacterial Proteins
  • Succinate Dehydrogenase