The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function |
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Authors: | Kim Jinoh Thanabalasuriar Ajitha Chaworth-Musters Tessa Fromme J Chris Frey Elizabeth A Lario Paula I Metalnikov Pavel Rizg Keyrillos Thomas Nikhil A Lee Sau Fung Hartland Elizabeth L Hardwidge Philip R Pawson Tony Strynadka Natalie C Finlay B Brett Schekman Randy Gruenheid Samantha |
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Institution: | Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA. |
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Abstract: | 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. |
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