Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo: role of mitochondrial associated protein (Map)
Back to previous page
| Authors: | Ma, CX; Wickham, ME; Guttman, JA; Deng, WY; Walker, J; Madsen, KL; Jacobson, K; Vogl, WA; Finlay, BB; Vallance, BA |
| Year: | 2006 |
| Journal: | Cell Microbiol. 8: 1669-1686 Article Link (DOI) |
| Title: | Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo: role of mitochondrial associated protein (Map) |
| Abstract: | Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli are non-invasive attach- ing/effacing (A/E) bacterial pathogens that infect their host’s intestinal epithelium, causing severe diar- rhoeal disease. These bacteria utilize a type III secre- tion 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 con- tributes to infection-induced epithelial barrier dys- function 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 colocal- ized with host cell mitochondria, and that in vivo infection led to a disruption of mitochondrial mor- phology in infected colonocytes as assessed by electron microscopy. Histochemical staining for the mitochondrial enzyme succinate dehydrogenase also revealed a significant loss of mitochondrial respira- tory function in the infected intestinal epithelium; however, both pathologies were attenuated in mice infected with a Dmap 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, dem- onstrating that Map contributes to the functional disruption of the intestinal epithelium during enteric infection by C. rodentium. |
Departmental members may update their publication list.