PXD047937

PXD047937 is an original dataset announced via ProteomeXchange.

Title	Theileria parasites sequester host eIF5a to escape elimination by host-mediated autophagy
Description	Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved sophisticated strategies to hijack host leukocytes, inducing proliferative and invasive phenotypes characteristic of cell transformation. Intracellular Theileria parasites secrete proteins into the host cell and recruit host proteins to induce oncogenic signaling for parasite survival. It is unknown how Theileria parasites evade host cell defense mechanisms, such as autophagy, to survive within host cells. Here, we show that Theileria annulata parasites sequester the host eIF5a protein to their surface to escape elimination by autophagic processes. We identified a small-molecule compound that reduces parasite load by inducing autophagic flux in host leukocytes, thereby uncoupling Theileria parasite survival from host cell survival. We took a chemical genetics approach to show that this compound induced host autophagy mechanisms and the formation of autophagic structures via AMPK activation and the release of the host protein eIF5A which is sequestered at the parasite surface. The sequestration of host eIF5a to the parasite surface offers a strategy to escape elimination by autophagic mechanisms. These results show how intracellular pathogens can avoid host defense mechanisms and identify a new anti-Theileria drug that induces autophagy to target parasite removal.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:42:42.831.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guillaume CHEVREUX
SpeciesList	scientific name: Theileria annulata; NCBI TaxID: 5874;
ModificationList	half cystine; phosphorylated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-19 03:33:08	ID requested
1	2024-05-24 02:51:43	announced
⏵ 2	2024-10-22 06:42:43	announced	2024-10-22: Updated project metadata.

10.1038/s41467-024-45022-7;

Villares M, Louren, ç, o N, Ktorza I, Berthelet J, Panagiotou A, Richard A, Amo A, Koziy Y, Medjkane S, Valente S, Fioravanti R, Pioche-Durieu C, Ligni, è, re L, Chevreux G, Mai A, Weitzman JB, Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy. Nat Commun, 15(1):2235(2024) [pubmed]

submitter keyword: Drug screening, Epigenetic inhibitor, Parasite host response, Theileria, Protein sequestration,Autophagy

Professor Jonathan Weitzman
contact affiliation	Université Paris Cité, CNRS, UMR7126 Epigenetics and Cell Fate, 75013 Paris, France
contact email	jonathan.weitzman@u-paris.fr
lab head
Guillaume CHEVREUX
contact affiliation	Institut Jacques Monod, CNRS UMR7592
contact email	guillaume.chevreux@ijm.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD047937

PRIDE project URI

• PRIDE
  1. PXD047937
     1. Label: PRIDE project
     2. Name: Theileria parasites sequester host eIF5a to escape elimination by host-mediated autophagy