title: The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function.
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.
authors.affiliation: Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jinoh
authors.initials: J
authors.lastname: Kim
authors.forename: Ajitha
authors.initials: A
authors.lastname: Thanabalasuriar
authors.forename: Tessa
authors.initials: T
authors.lastname: Chaworth-Musters
authors.forename: J Chris
authors.initials: JC
authors.lastname: Fromme
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Frey
authors.forename: Paula I
authors.initials: PI
authors.lastname: Lario
authors.forename: Pavel
authors.initials: P
authors.lastname: Metalnikov
authors.forename: Keyrillos
authors.initials: K
authors.lastname: Rizg
authors.forename: Nikhil A
authors.initials: NA
authors.lastname: Thomas
authors.forename: Sau Fung
authors.initials: SF
authors.lastname: Lee
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hartland
authors.forename: Philip R
authors.initials: PR
authors.lastname: Hardwidge
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Strynadka
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.forename: Randy
authors.initials: R
authors.lastname: Schekman
authors.forename: Samantha
authors.initials: S
authors.lastname: Gruenheid
mesh_terms: D000818:Animals; D016466:CHO Cells; D022181:COP-Coated Vesicles / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D054308:Enteropathogenic Escherichia coli / Q000472:pathogenicity / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D011506:Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D029968:Escherichia coli Proteins; C488216:NleA protein, E coli; D011506:Proteins; D033921:Vesicular Transport Proteins; D037521:Virulence Factors