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

Summary 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 Δ map 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 .