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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...

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Autores principales: Sá, Mónica, Costa, David Mendes, Teixeira, Ana Rafaela, Pérez-Cabezas, Begoña, Formaglio, Pauline, Golba, Sylvain, Sefiane-Djemaoune, Hélèna, Amino, Rogerio, Tavares, Joana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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