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 system to deliver the Tir effector molecule into host cells. In this paper, we show that the gene upstream of tir, orf19, encodes an additional type III secreted effector protein. Orf19 is delivered into host cells by a mechanism independent of endocytosis, but dependent on EspB. Orf19 is targeted to host mitochondria, where it appears to interfere with the ability to maintain membrane potential. Although the precise role of Orf19 remains to be elucidated, its interaction with mitochondria suggests a possible role in the subversion 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 protein targeted to mitochondria; it is probable that homologues (present in EPEC and Shigella species) and other bacterial effectors will also target this organelle.
Kenny
B
B
Department of Pathology and Microbiology, School of Medical Sciences, University Walk, Bristol, UK. B.Kenny@bristol.ac.uk
Jepson
M
M
D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics / Q000502:physiology
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C087863:EaeB protein, E coli; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; C401224:TrcA protein, E coli