Résumé
Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) maintain an extracellular lifestyle and use a type III secretion system to translocate effector proteins into the host cytosol. These effectors manipulate host pathways to favor bacterial replication and survival. NleA is an EHEC/EPEC- and related species-specific translocated effector protein that is essential for bacterial virulence. However, the mechanism by which NleA impacts virulence remains undetermined. Here we demonstrate that NleA compromises the Sec23/24 complex, a component of the mammalian COPII protein coat that shapes intracellular protein transport vesicles, by directly binding Sec24. Expression of an NleA-GFP fusion protein reduces the efficiency of cellular secretion by 50%, and secretion is inhibited in EPEC-infected cells. Direct biochemical experiments show that NleA inhibits COPII-dependent protein export from the endoplasmic reticulum. Collectively, these findings indicate that disruption of COPII function in host cells contributes to the virulence of EPEC and EHEC.
Langue d'origine | English |
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Pages (de-à) | 160-171 |
Nombre de pages | 12 |
Journal | Cell Host and Microbe |
Volume | 2 |
Numéro de publication | 3 |
DOI | |
Statut de publication | Published - sept. 13 2007 |
Publié à l'externe | Oui |
Note bibliographique
Funding Information:The authors wish to thank Jon Kagan for helpful discussions, Craig Roy for providing the SEAP plasmid, Jennifer Lippincott-Schwartz for providing the VSV-G plasmid, Matlashewski Lab for the use of the Tube Luminometer, Archana Srivastava and John Presley for advice regarding the VSV-G experiment, and Lei Zhu for technical assistance with animal experiments. S.G. is a Canada Research Chair in Bacterial Pathogenesis; R.S. is an Investigator of the HHMI; B.B.F. is a HHMI International Research Scholar, a CIHR Distinguished Investigator, and the UBC Peter Wall Distinguished Professor; N.C.S. is a HHMI International Scholar, CIHR Investigator, and MSFHR Senior Scholar; T.P. is a CIHR distinguished investigator; and P.I.L. is a CIHR fellow. E.L.H. is supported by grants from the ARC and NHMRC. S.F.L. is the recipient of a Monash Graduate Scholarship and a Monash International Postgraduate Research Scholarship. This project was supported through funding from CIHR operating grants to S.G., T.P., and B.B.F.; a Miller Foundation fellowship to J.C.F.; a Genome Canada Grant to T.P.; and support from the HHMI for N.C.S., B.B.F., and R.S.
ASJC Scopus Subject Areas
- Parasitology
- Microbiology
- Virology