TY - JOUR
T1 - The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function
AU - Kim, J
AU - Thanabalasuriar, Ajitha
AU - Chaworth-Musters, Tessa
AU - Fromme, J Chris
AU - Frey, Elizabeth A
AU - Lario, Paula I
AU - Metalnikov, Pavel
AU - Rizg, Keyrillos
AU - Thomas, Nikhil A
AU - Lee, Sau Fung
AU - Hartland, Elizabeth Louise
AU - Hardwidge, Philip R
AU - Pawson, Tony
AU - Strynadka, Natalie C
AU - Findlay, B Brett
AU - Schekman, Randy
AU - Gruenheid, Samantha
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18005731
M3 - Article
SN - 1931-3128
VL - 2
SP - 160
EP - 171
JO - Cell Host & Microbe
JF - Cell Host & Microbe
IS - 3
ER -