EspJ effector in enterohemorrhagic E. coli translocates into host mitochondria via an atypical mitochondrial targeting signal.
EHEC is a bacterial pathogen causing diarrhea and hemorrhagic colitis in humans. To exert virulence, EHEC exploits a subset of effectors that are translocated into host cells via the type III secretion system. EspJ, which was recently identified as a type III secreted effector, is conserved in related pathogens such as EPEC and Citrobacter rodentium. However, the exact function of EspJ remains unclear. In the present study, we found that EspJ was unstable in host cells, which might be attributable to the N-terminal part beginning from amino acid number 59. Using stable forms of EspJ derivatives, we demonstrated for the first time that EspJ has the ability to translocate into mitochondria via an atypical mitochondrial targeting signal at the N terminus (1-36 a.a.) of EspJ. It has been reported that a mitochondrial targeting effector, EspF, disrupts the mitochondrial membrane potential, resulting in an induction of host cell death. To further investigate EspJ function in mitochondria, HeLa cells were infected with wild-type EPEC, an isogenic EspJ-mutant or an EspJ-overexpressing strain. The result of LDH release assay using an EspJ-mutant showed that the EspJ effector appears not to be involved in cytotoxicity.
Kurushima
Jun
J
Laboratory of Bacterial Infection, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Nagai
Takeshi
T
Nagamatsu
Kanna
K
Abe
Akio
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D054324:Enterohemorrhagic Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D021381:Protein Transport
D029968:Escherichia coli Proteins; C497366:EspJ protein, E coli; D021382:Protein Sorting Signals