The key to egress? Babesia bovis perforin-like protein 1 (PLP1) with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell
Bovine babesiosis is a tick-borne disease caused by apicomplexan parasites of the Babesia genus that represents a major constraint to livestock production worldwide. Currently available vaccines are based on live parasites which have archetypal limitations. Our goal is to identify candidate antigens...
| Autores principales: | , , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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Elsevier
2022
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| Acceso en línea: | http://hdl.handle.net/20.500.12123/11813 https://www.sciencedirect.com/science/article/abs/pii/S0020751921001107 https://doi.org/10.1016/j.ijpara.2020.12.010 |
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| author | Paoletta, Martina Laughery, Jacob Michael Lopez Arias, Ludmila Sol Jaramillo Ortiz, Jose Montenegro, Valeria Noely Petrigh, Romina Ueti, Massaro W. Suarez, Carlos Esteban Farber, Marisa Diana Wilkowsky, Silvina Elizabeth |
| author_browse | Farber, Marisa Diana Jaramillo Ortiz, Jose Laughery, Jacob Michael Lopez Arias, Ludmila Sol Montenegro, Valeria Noely Paoletta, Martina Petrigh, Romina Suarez, Carlos Esteban Ueti, Massaro W. Wilkowsky, Silvina Elizabeth |
| author_facet | Paoletta, Martina Laughery, Jacob Michael Lopez Arias, Ludmila Sol Jaramillo Ortiz, Jose Montenegro, Valeria Noely Petrigh, Romina Ueti, Massaro W. Suarez, Carlos Esteban Farber, Marisa Diana Wilkowsky, Silvina Elizabeth |
| author_sort | Paoletta, Martina |
| collection | INTA Digital |
| description | Bovine babesiosis is a tick-borne disease caused by apicomplexan parasites of the Babesia genus that represents a major constraint to livestock production worldwide. Currently available vaccines are based on live parasites which have archetypal limitations. Our goal is to identify candidate antigens so that new and effective vaccines against Babesia may be developed. The perforin-like protein (PLP) family has been identified as a key player in cell traversal and egress in related apicomplexans and it was also identified in Babesia, but its function in this parasite remains unknown. The aim of this work was to define the PLP family in Babesia and functionally characterize PLP1, a representative member of the family in Babesia bovis. Bioinformatic analyses demonstrate a variable number of plp genes (four to eight) in the genomes of six different Babesia spp. and conservation of the family members at the secondary and tertiary structure levels. We demonstrate here that Babesia PLPs contain the critical domains present in other apicomplexan PLPs to display the lytic capacity. We then focused on the functional characterization of PLP1 of B. bovis, both in vitro and in vivo. PLP1 is expressed and exposed to the host immune system during infection and has high hemolytic capacity under a wide range of conditions in vitro. A B. bovis plp1 knockout line displayed a decreased growth rate in vitro compared with the wild type strain and a peculiar phenotype consisting of multiple parasites within a single red blood cell, although at low frequency. This phenotype suggests that the lack of PLP1 has a negative impact on the mechanism of egression of the parasite and, therefore, on its capacity to proliferate. It is possible that PLP1 is associated with other proteins in the processes of invasion and egress, which were found to have redundant mechanisms in related apicomplexans. Future work will be focused on unravelling the network of proteins involved in these essential parasite functions. |
| format | Artículo |
| id | INTA11813 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA118132022-05-05T17:48:38Z The key to egress? Babesia bovis perforin-like protein 1 (PLP1) with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell Paoletta, Martina Laughery, Jacob Michael Lopez Arias, Ludmila Sol Jaramillo Ortiz, Jose Montenegro, Valeria Noely Petrigh, Romina Ueti, Massaro W. Suarez, Carlos Esteban Farber, Marisa Diana Wilkowsky, Silvina Elizabeth Babesia bovis Transfección Hemólisis Bioinformática Transfection Haemolysis Bioinformatics Bovine babesiosis is a tick-borne disease caused by apicomplexan parasites of the Babesia genus that represents a major constraint to livestock production worldwide. Currently available vaccines are based on live parasites which have archetypal limitations. Our goal is to identify candidate antigens so that new and effective vaccines against Babesia may be developed. The perforin-like protein (PLP) family has been identified as a key player in cell traversal and egress in related apicomplexans and it was also identified in Babesia, but its function in this parasite remains unknown. The aim of this work was to define the PLP family in Babesia and functionally characterize PLP1, a representative member of the family in Babesia bovis. Bioinformatic analyses demonstrate a variable number of plp genes (four to eight) in the genomes of six different Babesia spp. and conservation of the family members at the secondary and tertiary structure levels. We demonstrate here that Babesia PLPs contain the critical domains present in other apicomplexan PLPs to display the lytic capacity. We then focused on the functional characterization of PLP1 of B. bovis, both in vitro and in vivo. PLP1 is expressed and exposed to the host immune system during infection and has high hemolytic capacity under a wide range of conditions in vitro. A B. bovis plp1 knockout line displayed a decreased growth rate in vitro compared with the wild type strain and a peculiar phenotype consisting of multiple parasites within a single red blood cell, although at low frequency. This phenotype suggests that the lack of PLP1 has a negative impact on the mechanism of egression of the parasite and, therefore, on its capacity to proliferate. It is possible that PLP1 is associated with other proteins in the processes of invasion and egress, which were found to have redundant mechanisms in related apicomplexans. Future work will be focused on unravelling the network of proteins involved in these essential parasite functions. Instituto de Biotecnología Fil: Paoletta, Martina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Paoletta, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Laughery, Jacob Michael. Washington State University. Department of Veterinary Microbiology and Pathology; Estados Unidos Fil: Lopez Arias, Ludmila Sol. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Lopez Arias, Ludmila Sol. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Jaramillo Ortiz, Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Jaramillo Ortiz, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Montenegro, Valeria Noely. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Montenegro, Valeria Noely. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Petrigh, Romina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Petrigh, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ueti, Massaro W. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology and Pathology; Estados Unidos Fil: Ueti, Massaro W. United States Department of Agricultural Research Service. Animal Disease Research Unit; Estados Unidos Fil: Suarez, Carlos Esteban. Washington State University. College of Veterinary Medicine. Department of Veterinary Microbiology and Pathology; Estados Unidos Fil: Suarez, Carlos Esteban. United States Department of Agricultural Research Service. Animal Disease Research Unit; Estados Unidos Fil: Farber, Marisa Diana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Farber, Marisa Diana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wilkowsky, Silvina Elizabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Wilkowsky, Silvina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2022-05-05T17:39:58Z 2022-05-05T17:39:58Z 2021-07 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/11813 https://www.sciencedirect.com/science/article/abs/pii/S0020751921001107 0020-7519 https://doi.org/10.1016/j.ijpara.2020.12.010 eng info:eu-repo/semantics/restrictedAccess application/pdf Elsevier International Journal for Parasitology 51 (8) : 643-658 (July 2021) |
| spellingShingle | Babesia bovis Transfección Hemólisis Bioinformática Transfection Haemolysis Bioinformatics Paoletta, Martina Laughery, Jacob Michael Lopez Arias, Ludmila Sol Jaramillo Ortiz, Jose Montenegro, Valeria Noely Petrigh, Romina Ueti, Massaro W. Suarez, Carlos Esteban Farber, Marisa Diana Wilkowsky, Silvina Elizabeth The key to egress? Babesia bovis perforin-like protein 1 (PLP1) with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell |
| title | The key to egress? Babesia bovis perforin-like protein 1 (PLP1) with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell |
| title_full | The key to egress? Babesia bovis perforin-like protein 1 (PLP1) with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell |
| title_fullStr | The key to egress? Babesia bovis perforin-like protein 1 (PLP1) with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell |
| title_full_unstemmed | The key to egress? Babesia bovis perforin-like protein 1 (PLP1) with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell |
| title_short | The key to egress? Babesia bovis perforin-like protein 1 (PLP1) with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell |
| title_sort | key to egress babesia bovis perforin like protein 1 plp1 with hemolytic capacity is required for blood stage replication and is involved in the exit of the parasite from the host cell |
| topic | Babesia bovis Transfección Hemólisis Bioinformática Transfection Haemolysis Bioinformatics |
| url | http://hdl.handle.net/20.500.12123/11813 https://www.sciencedirect.com/science/article/abs/pii/S0020751921001107 https://doi.org/10.1016/j.ijpara.2020.12.010 |
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