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| Status |
Public on Dec 19, 2023 |
| Title |
Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy |
| Organism |
Bos taurus |
| Experiment type |
Expression profiling by high throughput sequencing
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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.
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| Overall design |
5x10^6 cells (BL3 or TBL3) were used as starting material to extract RNA. In this dataset, we explore the transcriptomes of 4 conditions: - Uninfected BL3 cells - Theileria annulata-Infected TBL3 cells - BL3 cells, treated with MC2646 4μM, 24 hours - TBL3 cells, treated with MC2646 4μM, 24 hours
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/38472173/
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| Contributor(s) |
Villares M, Lourenço N, Ktorza I, Berthelet J, Panagiotou A, Richard A, Amo A, Koziy Y, Medjkane S, Valente S, Fioraventi R, Durieu C, Lignière L, Chevreux G, Mai A, Weitzman JB |
| Citation(s) |
38472173 |
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| Submission date |
Dec 13, 2023 |
| Last update date |
Mar 19, 2024 |
| Contact name |
Aristeidis Panagiotou |
| E-mail(s) |
aris_pan95@hotmail.com
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| Organization name |
CNRS
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| Department |
UMR7216 Epigenetics and Cell Fate
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| Lab |
Plasticity of Cellular Phenotypes
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| Street address |
35 Rue Hélène Brion
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| City |
Paris |
| ZIP/Postal code |
75013 |
| Country |
France |
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| Platforms (1) |
| GPL23055 |
Illumina NextSeq 500 (Bos taurus) |
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| Samples (12)
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| GSM7973686 |
TBL3 Cells, Untreated, Replicate 1 |
| GSM7973687 |
TBL3 Cells, Untreated, Replicate 2 |
| GSM7973688 |
TBL3 Cells, Untreated, Replicate 3 |
| GSM7973689 |
BL3 Cells, MC2646 Treated, Replicate 1 |
| GSM7973690 |
BL3 Cells, MC2646 Treated, Replicate 2 |
| GSM7973691 |
BL3 Cells, MC2646 Treated, Replicate 3 |
| GSM7973692 |
TBL3 Cells, MC2646 Treated, Replicate 1 |
| GSM7973693 |
TBL3 Cells, MC2646 Treated, Replicate 2 |
| GSM7973694 |
TBL3 Cells, MC2646 Treated, Replicate 3 |
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| Relations |
| BioProject |
PRJNA1052010 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE250088_Villares_GSEA.zip |
22.5 Mb |
(ftp)(http) |
ZIP |
| GSE250088_dea_Cheeseman_BL3_TBL3.tsv.gz |
1004.8 Kb |
(ftp)(http) |
TSV |
| GSE250088_dea_Cheeseman_TBL3_TBL3_Bup.tsv.gz |
1000.7 Kb |
(ftp)(http) |
TSV |
| GSE250088_dea_Villares_BL3_TBL3.tsv.gz |
961.3 Kb |
(ftp)(http) |
TSV |
| GSE250088_dea_Villares_TBL3_TBL3_2646.tsv.gz |
836.2 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
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