PXD023126-1

PXD023126 is an original dataset announced via ProteomeXchange.

Title	The type III secretion system effector EspO of enterohemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1
Description	Many 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.
HostingRepository	PRIDE
AnnounceDate	2021-10-15
AnnouncementXML	Submission_2021-10-15_03:48:30.437.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Wright
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-14 08:07:26	ID requested
⏵ 1	2021-10-15 03:48:30	announced

Dataset with its publication pending

submitter keyword: EspO, E.Coli, Human, MSMS

Jyoti Choudhary
contact affiliation	The Institute of Cancer Research
contact email	jyoti.choudhary@icr.ac.uk
lab head
James Wright
contact affiliation	The Institute of Cancer Research
contact email	james.wright@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023126
     1. Label: PRIDE project
     2. Name: The type III secretion system effector EspO of enterohemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1