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MAEBL Contributes to Plasmodium 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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146008/ https://www.ncbi.nlm.nih.gov/pubmed/35628522 http://dx.doi.org/10.3390/ijms23105711 |
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author | Sá, Mónica Costa, David Mendes Teixeira, Ana Rafaela Pérez-Cabezas, Begoña Formaglio, Pauline Golba, Sylvain Sefiane-Djemaoune, Hélèna Amino, Rogerio Tavares, Joana |
author_facet | Sá, Mónica Costa, David Mendes Teixeira, Ana Rafaela Pérez-Cabezas, Begoña Formaglio, Pauline Golba, Sylvain Sefiane-Djemaoune, Hélèna Amino, Rogerio Tavares, Joana |
author_sort | Sá, Mónica |
collection | PubMed |
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 Plasmodium sporozoites. Using transgenic parasites and live imaging in mice, we show that the absence of MAEBL reduces Plasmodium berghei hemolymph sporozoite infectivity to mice. Moreover, we found that maebl knockout (maebl-) 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 maebl- 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. |
format | Online Article Text |
id | pubmed-9146008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91460082022-05-29 MAEBL Contributes to Plasmodium Sporozoite Adhesiveness Sá, Mónica Costa, David Mendes Teixeira, Ana Rafaela Pérez-Cabezas, Begoña Formaglio, Pauline Golba, Sylvain Sefiane-Djemaoune, Hélèna Amino, Rogerio Tavares, Joana Int J Mol Sci Article 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 Plasmodium sporozoites. Using transgenic parasites and live imaging in mice, we show that the absence of MAEBL reduces Plasmodium berghei hemolymph sporozoite infectivity to mice. Moreover, we found that maebl knockout (maebl-) 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 maebl- 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. MDPI 2022-05-20 /pmc/articles/PMC9146008/ /pubmed/35628522 http://dx.doi.org/10.3390/ijms23105711 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sá, Mónica Costa, David Mendes Teixeira, Ana Rafaela Pérez-Cabezas, Begoña Formaglio, Pauline Golba, Sylvain Sefiane-Djemaoune, Hélèna Amino, Rogerio Tavares, Joana MAEBL Contributes to Plasmodium Sporozoite Adhesiveness |
title | MAEBL Contributes to Plasmodium Sporozoite Adhesiveness |
title_full | MAEBL Contributes to Plasmodium Sporozoite Adhesiveness |
title_fullStr | MAEBL Contributes to Plasmodium Sporozoite Adhesiveness |
title_full_unstemmed | MAEBL Contributes to Plasmodium Sporozoite Adhesiveness |
title_short | MAEBL Contributes to Plasmodium Sporozoite Adhesiveness |
title_sort | maebl contributes to plasmodium sporozoite adhesiveness |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146008/ https://www.ncbi.nlm.nih.gov/pubmed/35628522 http://dx.doi.org/10.3390/ijms23105711 |
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