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PXD023126

PXD023126 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe type III secretion system effector EspO of enterohemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1
DescriptionMany enteric pathogens employ a type III secretion system (T3SS) to translocate effector proteins directly into the host cell cytoplasm, where they subvert signaling pathways of the intestinal epithelium. Here, we report that the anti-apoptotic regulator HS1-associated protein X1 (HAX-1) is an interaction partner of the T3SS effectors EspO of enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium, OspE of Shigella flexneri and Osp1STYM of Salmonella enterica serovar Typhimurium. EspO, OspE and Osp1STYM have previously been reported to interact with the focal adhesions protein integrin linked kinase (ILK). We found that EspO localizes both to the focal adhesions (ILK localization) and mitochondria (HAX-1 localization), and that increased expression of HAX-1 leads to enhanced mitochondrial localization of EspO. Ectopic expression of EspO, OspE and Osp1STYM protects cells from apoptosis induced by staurosporine and tunicamycin. Depleting cells of HAX-1 indicates that the anti-apoptotic activity of EspO is HAX-1 dependent. Both HAX-1 and ILK were further confirmed as EspO1 interacting proteins during infection using T3SS-delivered EspO1. Using cell detachment as a proxy for cell death we confirmed that T3SS-delivered EspO1 could inhibit cell death induced during EPEC infection, to a similar extent as the anti-apoptotic effector NleH, or treatment with the pan caspase inhibitor z-VAD. In contrast, in cells lacking HAX-1, EspO1 was no longer able to protect against cell detachment, while NleH1 and z-VAD maintained their protective activity. Therefore during both infection and ectopic expression EspO protects cells from cell death by interacting with HAX-1. These results suggest that despite the differences between EHEC, C. rodentium, Shigella and S. Typhimurium infections, hijacking HAX-1 anti-apoptotic signaling is a common strategy to maintain the viability of infected cells.
HostingRepositoryPRIDE
AnnounceDate2021-10-15
AnnouncementXMLSubmission_2021-10-15_03:48:30.437.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJames Wright
SpeciesList scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-12-14 08:07:26ID requested
12021-10-15 03:48:30announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: EspO, E.Coli, Human, MSMS
Contact List
Jyoti Choudhary
contact affiliationThe Institute of Cancer Research
contact emailjyoti.choudhary@icr.ac.uk
lab head
James Wright
contact affiliationThe Institute of Cancer Research
contact emailjames.wright@icr.ac.uk
dataset submitter
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