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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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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. |
format | Online Article Text |
id | pubmed-9255738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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