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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.
  • Sá M; Host-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
  • Costa DM; Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal.
  • Teixeira AR; Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.
  • Pérez-Cabezas B; Host-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
  • Formaglio P; Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal.
  • Golba S; Host-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
  • Sefiane-Djemaoune H; Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal.
  • Amino R; Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.
  • Tavares J; Host-Parasite Interactions Group, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
Int J Mol Sci ; 23(10)2022 May 20.
Article in English | MEDLINE | ID: covidwho-1934114
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Plasmodium berghei / Protozoan Proteins / Receptors, Cell Surface Type of study: Prognostic study Topics: Vaccines Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23105711

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Plasmodium berghei / Protozoan Proteins / Receptors, Cell Surface Type of study: Prognostic study Topics: Vaccines Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23105711