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The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts

Plasmodium sporozoites that are transmitted by blood-feeding female Anopheles mosquitoes invade hepatocytes for an initial round of intracellular replication, leading to the release of merozoites that invade and multiply within red blood cells. Sporozoites and merozoites share a number of proteins t...

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Autores principales: Fernandes, Priyanka, Loubens, Manon, Le Borgne, Rémi, Marinach, Carine, Ardin, Béatrice, Briquet, Sylvie, Vincensini, Laetitia, Hamada, Soumia, Hoareau-Coudert, Bénédicte, Verbavatz, Jean-Marc, Weiner, Allon, Silvie, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255738/
https://www.ncbi.nlm.nih.gov/pubmed/35731833
http://dx.doi.org/10.1371/journal.ppat.1010643
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author Fernandes, Priyanka
Loubens, Manon
Le Borgne, Rémi
Marinach, Carine
Ardin, Béatrice
Briquet, Sylvie
Vincensini, Laetitia
Hamada, Soumia
Hoareau-Coudert, Bénédicte
Verbavatz, Jean-Marc
Weiner, Allon
Silvie, Olivier
author_facet Fernandes, Priyanka
Loubens, Manon
Le Borgne, Rémi
Marinach, Carine
Ardin, Béatrice
Briquet, Sylvie
Vincensini, Laetitia
Hamada, Soumia
Hoareau-Coudert, Bénédicte
Verbavatz, Jean-Marc
Weiner, Allon
Silvie, Olivier
author_sort Fernandes, Priyanka
collection PubMed
description Plasmodium sporozoites that are transmitted by blood-feeding female Anopheles mosquitoes invade hepatocytes for an initial round of intracellular replication, leading to the release of merozoites that invade and multiply within red blood cells. Sporozoites and merozoites share a number of proteins that are expressed by both stages, including the Apical Membrane Antigen 1 (AMA1) and the Rhoptry Neck Proteins (RONs). Although AMA1 and RONs are essential for merozoite invasion of erythrocytes during asexual blood stage replication of the parasite, their function in sporozoites was still unclear. Here we show that AMA1 interacts with RONs in mature sporozoites. By using DiCre-mediated conditional gene deletion in P. berghei, we demonstrate that loss of AMA1, RON2 or RON4 in sporozoites impairs colonization of the mosquito salivary glands and invasion of mammalian hepatocytes, without affecting transcellular parasite migration. Three-dimensional electron microscopy data showed that sporozoites enter salivary gland cells through a ring-like structure and by forming a transient vacuole. The absence of a functional AMA1-RON complex led to an altered morphology of the entry junction, associated with epithelial cell damage. Our data establish that AMA1 and RONs facilitate host cell invasion across Plasmodium invasive stages, and suggest that sporozoites use the AMA1-RON complex to efficiently and safely enter the mosquito salivary glands to ensure successful parasite transmission. These results open up the possibility of targeting the AMA1-RON complex for transmission-blocking antimalarial strategies.
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spelling pubmed-92557382022-07-06 The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts Fernandes, Priyanka Loubens, Manon Le Borgne, Rémi Marinach, Carine Ardin, Béatrice Briquet, Sylvie Vincensini, Laetitia Hamada, Soumia Hoareau-Coudert, Bénédicte Verbavatz, Jean-Marc Weiner, Allon Silvie, Olivier PLoS Pathog Research Article Plasmodium sporozoites that are transmitted by blood-feeding female Anopheles mosquitoes invade hepatocytes for an initial round of intracellular replication, leading to the release of merozoites that invade and multiply within red blood cells. Sporozoites and merozoites share a number of proteins that are expressed by both stages, including the Apical Membrane Antigen 1 (AMA1) and the Rhoptry Neck Proteins (RONs). Although AMA1 and RONs are essential for merozoite invasion of erythrocytes during asexual blood stage replication of the parasite, their function in sporozoites was still unclear. Here we show that AMA1 interacts with RONs in mature sporozoites. By using DiCre-mediated conditional gene deletion in P. berghei, we demonstrate that loss of AMA1, RON2 or RON4 in sporozoites impairs colonization of the mosquito salivary glands and invasion of mammalian hepatocytes, without affecting transcellular parasite migration. Three-dimensional electron microscopy data showed that sporozoites enter salivary gland cells through a ring-like structure and by forming a transient vacuole. The absence of a functional AMA1-RON complex led to an altered morphology of the entry junction, associated with epithelial cell damage. Our data establish that AMA1 and RONs facilitate host cell invasion across Plasmodium invasive stages, and suggest that sporozoites use the AMA1-RON complex to efficiently and safely enter the mosquito salivary glands to ensure successful parasite transmission. These results open up the possibility of targeting the AMA1-RON complex for transmission-blocking antimalarial strategies. Public Library of Science 2022-06-22 /pmc/articles/PMC9255738/ /pubmed/35731833 http://dx.doi.org/10.1371/journal.ppat.1010643 Text en © 2022 Fernandes et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Fernandes, Priyanka
Loubens, Manon
Le Borgne, Rémi
Marinach, Carine
Ardin, Béatrice
Briquet, Sylvie
Vincensini, Laetitia
Hamada, Soumia
Hoareau-Coudert, Bénédicte
Verbavatz, Jean-Marc
Weiner, Allon
Silvie, Olivier
The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts
title The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts
title_full The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts
title_fullStr The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts
title_full_unstemmed The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts
title_short The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts
title_sort ama1-ron complex drives plasmodium sporozoite invasion in the mosquito and mammalian hosts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255738/
https://www.ncbi.nlm.nih.gov/pubmed/35731833
http://dx.doi.org/10.1371/journal.ppat.1010643
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