1. The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function.
- Author
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Kim J, Thanabalasuriar A, Chaworth-Musters T, Fromme JC, Frey EA, Lario PI, Metalnikov P, Rizg K, Thomas NA, Lee SF, Hartland EL, Hardwidge PR, Pawson T, Strynadka NC, Finlay BB, Schekman R, and Gruenheid S
- Subjects
- Animals, CHO Cells, Cricetinae, Cricetulus, Enteropathogenic Escherichia coli pathogenicity, HeLa Cells, Humans, COP-Coated Vesicles metabolism, Enteropathogenic Escherichia coli physiology, Escherichia coli Proteins physiology, Proteins metabolism, Vesicular Transport Proteins metabolism, Virulence Factors physiology
- 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.
- Published
- 2007
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