Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo: role of mitochondrial associated protein (Map).
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.
Ma
Caixia
C
Division of Gastroenterology, BC's Children's Hospital, Vancouver, BC, Canada.
Wickham
Mark E
ME
Guttman
Julian A
JA
Deng
Wanyin
W
Walker
John
J
Madsen
Karen L
KL
Jacobson
Kevan
K
Vogl
Wayne A
WA
Finlay
B Brett
BB
Vallance
Bruce A
BA
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D044082:Citrobacter rodentium / Q000472:pathogenicity / Q000502:physiology*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D004756:Enterobacteriaceae Infections / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology*; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051336:Mitochondrial Membranes; D013385:Succinate Dehydrogenase / Q000378:metabolism
D001426:Bacterial Proteins; D013385:Succinate Dehydrogenase