MAEBL Contributes to <i>Plasmodium</i> Sporozoite Adhesiveness
The sole currently approved malaria vaccine targets the circumsporozoite protein—the protein that densely coats the surface of sporozoites, the parasite stage deposited in the skin of the mammalian host by infected mosquitoes. However, this vaccine only confers moderate protection against clinical d...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/10/5711 |
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| author | Mónica Sá David Mendes Costa Ana Rafaela Teixeira Begoña Pérez-Cabezas Pauline Formaglio Sylvain Golba Hélèna Sefiane-Djemaoune Rogerio Amino Joana Tavares |
| author_facet | Mónica Sá David Mendes Costa Ana Rafaela Teixeira Begoña Pérez-Cabezas Pauline Formaglio Sylvain Golba Hélèna Sefiane-Djemaoune Rogerio Amino Joana Tavares |
| author_sort | Mónica Sá |
| collection | DOAJ |
| description | The sole currently approved malaria vaccine targets the circumsporozoite protein—the protein that densely coats the surface of sporozoites, the parasite stage deposited in the skin of the mammalian host by infected mosquitoes. However, this vaccine only confers moderate protection against clinical diseases in children, impelling a continuous search for novel candidates. In this work, we studied the importance of the membrane-associated erythrocyte binding-like protein (MAEBL) for infection by <i>Plasmodium</i> sporozoites. Using transgenic parasites and live imaging in mice, we show that the absence of MAEBL reduces <i>Plasmodium berghei</i> hemolymph sporozoite infectivity to mice. Moreover, we found that <i>maebl</i> knockout (<i>maebl</i>-) sporozoites display reduced adhesion, including to cultured hepatocytes, which could contribute to the defects in multiple biological processes, such as in gliding motility, hepatocyte wounding, and invasion. The <i>maebl</i>- defective phenotypes in mosquito salivary gland and liver infection were reverted by genetic complementation. Using a parasite line expressing a C-terminal myc-tagged MAEBL, we found that MAEBL levels peak in midgut and hemolymph parasites but drop after sporozoite entry into the salivary glands, where the labeling was found to be heterogeneous among sporozoites. MAEBL was found associated, not only with micronemes, but also with the surface of mature sporozoites. Overall, our data provide further insight into the role of MAEBL in sporozoite infectivity and may contribute to the design of future immune interventions. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:43:42Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b16787704b8b4bb8bb42deaf533031f62023-11-23T11:27:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310571110.3390/ijms23105711MAEBL Contributes to <i>Plasmodium</i> Sporozoite AdhesivenessMónica Sá0David Mendes Costa1Ana Rafaela Teixeira2Begoña Pérez-Cabezas3Pauline Formaglio4Sylvain Golba5Hélèna Sefiane-Djemaoune6Rogerio Amino7Joana Tavares8Host-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalHost-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalHost-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalHost-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalUnit of Malaria Infection and Immunity, Institut Pasteur, 75015 Paris, FranceCenter for Production and Infection of <i>Anopheles</i>, Institut Pasteur, 75015 Paris, FranceCenter for Production and Infection of <i>Anopheles</i>, Institut Pasteur, 75015 Paris, FranceUnit of Malaria Infection and Immunity, Institut Pasteur, 75015 Paris, FranceHost-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalThe sole currently approved malaria vaccine targets the circumsporozoite protein—the protein that densely coats the surface of sporozoites, the parasite stage deposited in the skin of the mammalian host by infected mosquitoes. However, this vaccine only confers moderate protection against clinical diseases in children, impelling a continuous search for novel candidates. In this work, we studied the importance of the membrane-associated erythrocyte binding-like protein (MAEBL) for infection by <i>Plasmodium</i> sporozoites. Using transgenic parasites and live imaging in mice, we show that the absence of MAEBL reduces <i>Plasmodium berghei</i> hemolymph sporozoite infectivity to mice. Moreover, we found that <i>maebl</i> knockout (<i>maebl</i>-) sporozoites display reduced adhesion, including to cultured hepatocytes, which could contribute to the defects in multiple biological processes, such as in gliding motility, hepatocyte wounding, and invasion. The <i>maebl</i>- defective phenotypes in mosquito salivary gland and liver infection were reverted by genetic complementation. Using a parasite line expressing a C-terminal myc-tagged MAEBL, we found that MAEBL levels peak in midgut and hemolymph parasites but drop after sporozoite entry into the salivary glands, where the labeling was found to be heterogeneous among sporozoites. MAEBL was found associated, not only with micronemes, but also with the surface of mature sporozoites. Overall, our data provide further insight into the role of MAEBL in sporozoite infectivity and may contribute to the design of future immune interventions.https://www.mdpi.com/1422-0067/23/10/5711<i>Plasmodium</i>sporozoiteMAEBLliveradhesiongenetic complementation |
| spellingShingle | Mónica Sá David Mendes Costa Ana Rafaela Teixeira Begoña Pérez-Cabezas Pauline Formaglio Sylvain Golba Hélèna Sefiane-Djemaoune Rogerio Amino Joana Tavares MAEBL Contributes to <i>Plasmodium</i> Sporozoite Adhesiveness International Journal of Molecular Sciences <i>Plasmodium</i> sporozoite MAEBL liver adhesion genetic complementation |
| title | MAEBL Contributes to <i>Plasmodium</i> Sporozoite Adhesiveness |
| title_full | MAEBL Contributes to <i>Plasmodium</i> Sporozoite Adhesiveness |
| title_fullStr | MAEBL Contributes to <i>Plasmodium</i> Sporozoite Adhesiveness |
| title_full_unstemmed | MAEBL Contributes to <i>Plasmodium</i> Sporozoite Adhesiveness |
| title_short | MAEBL Contributes to <i>Plasmodium</i> Sporozoite Adhesiveness |
| title_sort | maebl contributes to i plasmodium i sporozoite adhesiveness |
| topic | <i>Plasmodium</i> sporozoite MAEBL liver adhesion genetic complementation |
| url | https://www.mdpi.com/1422-0067/23/10/5711 |
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