Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria

Many Gram-negative pathogens use a type III secretion apparatus to deliver effector molecules into host cells to subvert cellular processes in favour of the pathogen. Enteropathogenic Escherichia coli (EPEC) uses such a syste m to deliver the Tir effector molecule into host cells. In this paper, we s how that the gene upstream of tir, orf19, encodes an additional type III se creted effector protein. Orf19 is delivered into host cells by a mechanism independent of endocytosis, but dependent on EspB. Orf19 is targeted to hos t mitochondria, where it appears to interfere with the ability to maintain membrane potential. Although the precise role of Orf19 remains to be elucid ated, its interaction with mitochondria suggests a possible role in the sub version of key functions of these organelles, such as energy production or control of cell death. This is the first example of a type III secreted pro tein targeted to mitochondria; it is probable that homologues (present in E PEC and Shigella species) and other bacterial effecters will also target th is organelle.