MMV560185 from pathogen box induces extrinsic pathway of apoptosis in Theileria annulata infected bovine leucocytes

Araveti, Prasanna Babu; Macha, Vijay; Kar, Prajna Parimita; Varunan, Shalu M.; Srivastava, Anand

doi:10.1016/j.ijpddr.2021.12.003

Cited by 5 publications

(4 citation statements)

References 49 publications

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“…The in-house-established T. annulata -infected bovine leucocyte (Ana2014 cells) culture was maintained as described previously ( 36 , 37 ). Briefly, T. annulata -infected bovine leucocytes were cultured in RPMI 1640 (Gibco, Life Technologies) reconstituted with 10% heat-inactivated fetal bovine serum (GE Healthcare) and 100 μg/mL penicillin-streptomycin (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Identification of a Novel Interaction between Theileria Prohibitin ( Ta PHB-1) and Bovine RuvB-Like AAA ATPase 1

et al. 2023

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Section: Methodsmentioning

confidence: 99%

Identification of a Novel Interaction between Theileria Prohibitin ( Ta PHB-1) and Bovine RuvB-Like AAA ATPase 1

et al. 2023

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“…The in-house established T. annulata infected bovine leucocytes (Ana2014 cells) culture was maintained as described previously (42, 43). Briefly, T. annulata infected bovine leucocytes were cultured in RPMI 1640 (Gibco, Life technologies) reconstituted with 10% heat inactivated fetal bovine serum (GE healthcare) and 100 μg/ml penicillin-streptomycin (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Identification of a novel interaction between Theileria Prohibitin (TaPHB-1) and bovine RUVBL-1

Araveti

Kar

Kuriakose³

et al. 2022

Preprint

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Bovine tropical theileriosis causes huge economic loss worldwide. It is a tick borne disease of bovine caused by the parasite Theileria annulata. T. annulata is an intracellular parasite that belongs to the phylum Apicomplexa.The sporozoites of T. annulata re released by the tick into the bloodstream of the host during the blood meal that invades bovine B cells, macrophages, or monocytes. This infection leads to the transformation of the host cells and brings cancer-like phenotype in the host cells. The parasite proteins play a vital role in the transformation of the host cell. However, the parasite factors involved in the host cell transformation are not well explored. Previously, Ta PIN1, a peptidyl-prolyl isomerase of T. annulata, was shown to be secreted to the host cytosol and play a role in the host cell transformation. The present study was carried out to explore the parasite-host interactions that may play an important role in the host cell transformation. We identified the parasite proteins that are expressed in the schizont stage with a signal peptide. We narrow down our search to a parasite prohibitin. The in silico analysis of T. annulata prohibitin (TA04375, Ta PHB-1) showed that Ta PHB-1 shares homology with the mammalian prohibitin 1. With the localization experiments, we confirmed that Ta PHB-1 is exported to the parasite surface and also to the host cell cytosol. Further, we observed that the localization of host prohibitin differs in the parasite-infected cells and could not be reverted back by the elimination of the parasite in the infected cells. We found through the yeast-two-hybrid studies that bovine RUVBL1 (BoRUVBL-1) interacts with Ta PHB-1. The interaction between BoRUVBL1 and Ta PHB-1 was predominantly observed on the parasite surface in the infected bovine cells. The interaction was further confirmed with immunoprecipitation and LC-MS/MS analysis. Further, the LC-MS/MS based Ta PHB-1 interactome study reveals that it interacts with proteins that regulate actin cytoskeleton organization, protein folding, mRNA processing, and metabolic processes. Our finding suggests that the parasite releases prohibitin protein into the cytoplasm of the host cell where it interacts with the host RUVBL-1. This finding has implications not only in the understanding of Theileria parasite biology in greater depth but also in the cancer biology where previously differential localization of prohibitin proteins was observed but its interaction partner was not known.

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“…It is the only drug used for treating bovine theileriosis (BT). However, reports of treatment failure have surfaced recently, pointing to the need for alternative treatments to curtail the disease [ 7 – 9 ]. Hence, there is an urgent need to identify new drugs and targets for treating BT [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Artemisinin derivatives induce oxidative stress leading to DNA damage and caspase-mediated apoptosis in Theileria annulata-transformed cells

et al. 2023

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Background Bovine theileriosis caused by the eukaryotic parasite Theileria annulata is an economically important tick-borne disease. If it is not treated promptly, this lymphoproliferative disease has a significant fatality rate. Buparvaquone (BPQ) is the only chemotherapy-based treatment available right now. However, with the emergence of BPQ resistance on the rise and no backup therapy available, it is critical to identify imperative drugs and new targets against Theileria parasites. Methods Artemisinin and its derivatives artesunate (ARS), artemether (ARM), or dihydroartemisinin (DHART) are the primary defence line against malaria parasites. This study has analysed artemisinin and its derivatives for their anti-Theilerial activity and mechanism of action. Results ARS and DHART showed potent activity against the Theileria-infected cells. BPQ in combination with ARS or DHART showed a synergistic effect. The compounds act specifically on the parasitised cells and have minimal cytotoxicity against the uninfected host cells. Treatment with ARS or DHART induces ROS-mediated oxidative DNA damage leading to cell death. Further blocking intracellular ROS by its scavengers antagonised the anti-parasitic activity of the compounds. Increased ROS production induces oxidative stress and DNA damage causing p53 activation followed by caspase-dependent apoptosis in the Theileria-infected cells. Conclusions Our findings give unique insights into the previously unknown molecular pathways underpinning the anti-Theilerial action of artemisinin derivatives, which may aid in formulating new therapies against this deadly parasite.

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MMV560185 from pathogen box induces extrinsic pathway of apoptosis in Theileria annulata infected bovine leucocytes

Cited by 5 publications

References 49 publications

Identification of a Novel Interaction between Theileria Prohibitin ( Ta PHB-1) and Bovine RuvB-Like AAA ATPase 1

Identification of a Novel Interaction between Theileria Prohibitin ( Ta PHB-1) and Bovine RuvB-Like AAA ATPase 1

Identification of a novel interaction between Theileria Prohibitin (TaPHB-1) and bovine RUVBL-1

Artemisinin derivatives induce oxidative stress leading to DNA damage and caspase-mediated apoptosis in Theileria annulata-transformed cells

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