Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in Sudan
The tick-borne parasite Theileria annulata is the causative agent of tropical theileriosis or Mediterranean theileriosis. Infection of bovine leukocytes by the obligate intracellular parasites induces proliferative and invasive phenotypes associated with activated signaling pathways. The transformed...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-12-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320719301411 |
| _version_ | 1818135726391296000 |
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| author | Bashir Salim Elisha Chatanga Guillaume Jannot Ehab Mossaad Ryo Nakao Jonathan B. Weitzman |
| author_facet | Bashir Salim Elisha Chatanga Guillaume Jannot Ehab Mossaad Ryo Nakao Jonathan B. Weitzman |
| author_sort | Bashir Salim |
| collection | DOAJ |
| description | The tick-borne parasite Theileria annulata is the causative agent of tropical theileriosis or Mediterranean theileriosis. Infection of bovine leukocytes by the obligate intracellular parasites induces proliferative and invasive phenotypes associated with activated signaling pathways. The transformed phenotypes of infected cells are reversible by treatment with the theilericidal drug buparvaquone. Recent reports of resistance to buparvaquone in Africa and Asia highlight the need to investigate the mechanisms and prevalence of drug resistance. We screened 67 T. annulata isolates from Sudan to investigate mutations in the T. annulata prolyl isomerase I gene (TaPIN1). The secreted TaPin1 interacts with host proteins to induce pathways driving oncogenic transformation and metabolic reprogramming. We found an Alanine-to-Proline mutation at position 53 (A53P) in the catalytic loop that was previously found in Tunisian drug-resistant samples. This is the first study reporting independent confirmation of the A53P mutation in geographically isolated samples. We found several additional mutations in the predicted N-terminal signal peptide that might affect TaPin1 processing or targeting. We found that many parasites also share mutations in both the TaPIN1 and the cytochrome b genes, suggesting that these two genes represent important biomarkers to follow the spread of resistance in Africa, the Middle East and Asia. Keywords: Drug-resistance, Prolyl isomerization, Point mutations, Markers, Theileria, Theileriosis |
| first_indexed | 2024-12-11T09:29:05Z |
| format | Article |
| id | doaj.art-efdfc87d9b604781919a12caf4f7516e |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-12-11T09:29:05Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-efdfc87d9b604781919a12caf4f7516e2022-12-22T01:13:04ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072019-12-0111101105Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in SudanBashir Salim0Elisha Chatanga1Guillaume Jannot2Ehab Mossaad3Ryo Nakao4Jonathan B. Weitzman5Department of Parasitology, Faculty of Veterinary Medicine, University of Khartoum, P.O. Box 32, Khartoum North, Sudan; Corresponding author.Laboratory of Parasitology, Graduate School of Infectious Diseases, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Sapporo, Hokkaido, 060-0818, JapanUniversité de Paris, Epigenetics and Cell Fate, CNRS, F-75013, Paris, FranceDepartment of Pathology, Parasitology and Microbiology, College of Veterinary Medicine, Sudan University of Science and Technology, P.O. Box 204, Khartoum, SudanLaboratory of Parasitology, Graduate School of Infectious Diseases, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Sapporo, Hokkaido, 060-0818, JapanUniversité de Paris, Epigenetics and Cell Fate, CNRS, F-75013, Paris, France; Corresponding author.The tick-borne parasite Theileria annulata is the causative agent of tropical theileriosis or Mediterranean theileriosis. Infection of bovine leukocytes by the obligate intracellular parasites induces proliferative and invasive phenotypes associated with activated signaling pathways. The transformed phenotypes of infected cells are reversible by treatment with the theilericidal drug buparvaquone. Recent reports of resistance to buparvaquone in Africa and Asia highlight the need to investigate the mechanisms and prevalence of drug resistance. We screened 67 T. annulata isolates from Sudan to investigate mutations in the T. annulata prolyl isomerase I gene (TaPIN1). The secreted TaPin1 interacts with host proteins to induce pathways driving oncogenic transformation and metabolic reprogramming. We found an Alanine-to-Proline mutation at position 53 (A53P) in the catalytic loop that was previously found in Tunisian drug-resistant samples. This is the first study reporting independent confirmation of the A53P mutation in geographically isolated samples. We found several additional mutations in the predicted N-terminal signal peptide that might affect TaPin1 processing or targeting. We found that many parasites also share mutations in both the TaPIN1 and the cytochrome b genes, suggesting that these two genes represent important biomarkers to follow the spread of resistance in Africa, the Middle East and Asia. Keywords: Drug-resistance, Prolyl isomerization, Point mutations, Markers, Theileria, Theileriosishttp://www.sciencedirect.com/science/article/pii/S2211320719301411 |
| spellingShingle | Bashir Salim Elisha Chatanga Guillaume Jannot Ehab Mossaad Ryo Nakao Jonathan B. Weitzman Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in Sudan International Journal for Parasitology: Drugs and Drug Resistance |
| title | Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in Sudan |
| title_full | Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in Sudan |
| title_fullStr | Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in Sudan |
| title_full_unstemmed | Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in Sudan |
| title_short | Mutations in the TaPIN1 peptidyl prolyl isomerase gene in Theileria annulata parasites isolated in Sudan |
| title_sort | mutations in the tapin1 peptidyl prolyl isomerase gene in theileria annulata parasites isolated in sudan |
| url | http://www.sciencedirect.com/science/article/pii/S2211320719301411 |
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