The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function.
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.
Kim
Jinoh
J
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Thanabalasuriar
Ajitha
A
Chaworth-Musters
Tessa
T
Fromme
J Chris
JC
Frey
Elizabeth A
EA
Lario
Paula I
PI
Metalnikov
Pavel
P
Rizg
Keyrillos
K
Thomas
Nikhil A
NA
Lee
Sau Fung
SF
Hartland
Elizabeth L
EL
Hardwidge
Philip R
PR
Pawson
Tony
T
Strynadka
Natalie C
NC
Finlay
B Brett
BB
Schekman
Randy
R
Gruenheid
Samantha
S
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*
D029968:Escherichia coli Proteins; C488216:NleA protein, E coli; D011506:Proteins; D033921:Vesicular Transport Proteins; D037521:Virulence Factors