First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins
Cholesterol is a molecule vital for tick physiology, but ticks cannot synthesize it and rely on dietary cholesterol. Therefore, tick proteins involved in cholesterol absorption and transport, such as the Niemann-Pick type C1 domain-containing (NPC1) proteins, are promising targets for anti-tick vacc...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-11-01
|
| Series: | Ticks and Tick-Borne Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1877959X2400075X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850261298557747200 |
|---|---|
| author | Lucía de Dios-Blázquez Ana Laura Cano-Argüelles Ricardo Pérez-Sánchez María González-Sánchez Ana Oleaga |
| author_facet | Lucía de Dios-Blázquez Ana Laura Cano-Argüelles Ricardo Pérez-Sánchez María González-Sánchez Ana Oleaga |
| author_sort | Lucía de Dios-Blázquez |
| collection | DOAJ |
| description | Cholesterol is a molecule vital for tick physiology, but ticks cannot synthesize it and rely on dietary cholesterol. Therefore, tick proteins involved in cholesterol absorption and transport, such as the Niemann-Pick type C1 domain-containing (NPC1) proteins, are promising targets for anti-tick vaccine development. The aim of this study was to assess the structure, function, and protective efficacy of the NPC1 orthologues identified previously in the midgut transcriptomes of argasid ticks Ornithodoros erraticus and Ornithodoros moubata. For this purpose, their corresponding cDNA coding sequences were cloned and sequenced, their secondary and 3D structures were predicted, and their function was evaluated through RNAi-mediated gene knockdown and in vitro feeding on blood supplemented with ezetimibe, which inhibits cholesterol binding by NPC1 proteins. Subsequently, the protective efficacy of a recombinant form of NPC1 from O. moubata (rOmNPC1) was tested in a rabbit vaccine trial. While inhibiting cholesterol absorption with ezetimibe resulted in up to 77 % mortality in adult O. moubata, NPC1 gene knockdown and vaccination with rOmNPC1 decreased female reproductive performance in terms of the number and fertility of laid eggs. This study presents the initial molecular and functional insights into NPC1 proteins in soft ticks and supports the hypothesis that disrupting cholesterol metabolism diminishes tick viability and reproduction, rendering Niemann-Pick type C1 domain-containing proteins promising targets for drugs or vaccines. |
| format | Article |
| id | doaj-art-65cd9ffdc09e4da39f0962588cbf6999 |
| institution | OA Journals |
| issn | 1877-9603 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ticks and Tick-Borne Diseases |
| spelling | doaj-art-65cd9ffdc09e4da39f0962588cbf69992025-08-20T01:55:27ZengElsevierTicks and Tick-Borne Diseases1877-96032024-11-0115610238210.1016/j.ttbdis.2024.102382First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteinsLucía de Dios-Blázquez0Ana Laura Cano-Argüelles1Ricardo Pérez-Sánchez2María González-Sánchez3Ana Oleaga4Fundación para la Investigación Biomédica del Hospital Universitario la Paz -FIBHULP-, Paseo de la Castellana, 261, 28046, Madrid, SpainParasitology, Institute of Natural Resources and Agrobiology of Salamanca (IRNASA, CSIC), Cordel de Merinas, 40-52, 37008, Salamanca, SpainParasitology, Institute of Natural Resources and Agrobiology of Salamanca (IRNASA, CSIC), Cordel de Merinas, 40-52, 37008, Salamanca, SpainParasitology, Institute of Natural Resources and Agrobiology of Salamanca (IRNASA, CSIC), Cordel de Merinas, 40-52, 37008, Salamanca, SpainFundación para la Investigación Biomédica del Hospital Universitario la Paz -FIBHULP-, Paseo de la Castellana, 261, 28046, Madrid, Spain; Corresponding author at: Parasitology Laboratory, Institute of Natural Resources and Agrobiology of Salamanca (IRNASA, CSIC), Cordel de Merinas, 40-52, 37008, Salamanca, Spain.Cholesterol is a molecule vital for tick physiology, but ticks cannot synthesize it and rely on dietary cholesterol. Therefore, tick proteins involved in cholesterol absorption and transport, such as the Niemann-Pick type C1 domain-containing (NPC1) proteins, are promising targets for anti-tick vaccine development. The aim of this study was to assess the structure, function, and protective efficacy of the NPC1 orthologues identified previously in the midgut transcriptomes of argasid ticks Ornithodoros erraticus and Ornithodoros moubata. For this purpose, their corresponding cDNA coding sequences were cloned and sequenced, their secondary and 3D structures were predicted, and their function was evaluated through RNAi-mediated gene knockdown and in vitro feeding on blood supplemented with ezetimibe, which inhibits cholesterol binding by NPC1 proteins. Subsequently, the protective efficacy of a recombinant form of NPC1 from O. moubata (rOmNPC1) was tested in a rabbit vaccine trial. While inhibiting cholesterol absorption with ezetimibe resulted in up to 77 % mortality in adult O. moubata, NPC1 gene knockdown and vaccination with rOmNPC1 decreased female reproductive performance in terms of the number and fertility of laid eggs. This study presents the initial molecular and functional insights into NPC1 proteins in soft ticks and supports the hypothesis that disrupting cholesterol metabolism diminishes tick viability and reproduction, rendering Niemann-Pick type C1 domain-containing proteins promising targets for drugs or vaccines.http://www.sciencedirect.com/science/article/pii/S1877959X2400075XTickArgasidOrnithodorosNiemann-Pick type C1 proteinsCholesterol |
| spellingShingle | Lucía de Dios-Blázquez Ana Laura Cano-Argüelles Ricardo Pérez-Sánchez María González-Sánchez Ana Oleaga First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins Ticks and Tick-Borne Diseases Tick Argasid Ornithodoros Niemann-Pick type C1 proteins Cholesterol |
| title | First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins |
| title_full | First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins |
| title_fullStr | First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins |
| title_full_unstemmed | First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins |
| title_short | First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins |
| title_sort | first data on cholesterol metabolism in ornithodoros argasid ticks molecular and functional characterization of the n terminal domain of niemann pick c1 proteins |
| topic | Tick Argasid Ornithodoros Niemann-Pick type C1 proteins Cholesterol |
| url | http://www.sciencedirect.com/science/article/pii/S1877959X2400075X |
| work_keys_str_mv | AT luciadediosblazquez firstdataoncholesterolmetabolisminornithodorosargasidticksmolecularandfunctionalcharacterizationofthenterminaldomainofniemannpickc1proteins AT analauracanoarguelles firstdataoncholesterolmetabolisminornithodorosargasidticksmolecularandfunctionalcharacterizationofthenterminaldomainofniemannpickc1proteins AT ricardoperezsanchez firstdataoncholesterolmetabolisminornithodorosargasidticksmolecularandfunctionalcharacterizationofthenterminaldomainofniemannpickc1proteins AT mariagonzalezsanchez firstdataoncholesterolmetabolisminornithodorosargasidticksmolecularandfunctionalcharacterizationofthenterminaldomainofniemannpickc1proteins AT anaoleaga firstdataoncholesterolmetabolisminornithodorosargasidticksmolecularandfunctionalcharacterizationofthenterminaldomainofniemannpickc1proteins |