Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy

Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy

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...

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Bibliographic Details
Published in:Nature communications Vol. 15; no. 1; p. 2235
Main Authors: Villares, Marie, Lourenço, Nelly, Ktorza, Ivan, Berthelet, Jérémy, Panagiotou, Aristeidis, Richard, Aurélie, Amo, Angélique, Koziy, Yulianna, Medjkane, Souhila, Valente, Sergio, Fioravanti, Rossella, Pioche-Durieu, Catherine, Lignière, Laurent, Chevreux, Guillaume, Mai, Antonello, Weitzman, Jonathan B.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 12-03-2024
Nature Publishing Group
Nature Portfolio
Subjects:
13/31
13/89
38/91
631/326/417/2546
631/80/39
692/699/255/1715
82/47
82/58
82/80
96/106
96/109
96/63
96/98
Animals
Autophagy
Cattle
Cell survival
Defense mechanisms
Developing countries
Genetics
Host-Parasite Interactions - physiology
Humanities and Social Sciences
Intracellular
LDCs
Leukocytes
Life Sciences
multidisciplinary
Parasites
Pathogens
Phenotypes
Proteins
Science
Science (multidisciplinary)
Signal Transduction
Survival
Theileria
Theileria - genetics
Theileriasis - parasitology
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Summary: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. Theileria parasites have evolved mechanisms to evade host cell defenses. Here, Villares et al use an anti-parasite drug to show how intracellular parasites sequester host eIF5A to escape elimination by autophagy pathways.
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content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-45022-7