The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts - Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé - UMS 37 PASS Access content directly
Journal Articles PLoS Pathogens Year : 2022

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

Abstract

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.

Domains

Parasitology
Fichier principal
Vignette du fichier
Fernandes_Loubens_revision_FINAL.pdf (61.66 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03704136 , version 1 (24-06-2022)

Identifiers

Cite

Priyanka Fernandes, Manon Loubens, Rémi Le Borgne, Carine Marinach, Beatrice Ardin, et al.. The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts. PLoS Pathogens, 2022, 18 (6), pp.e1010643. ⟨10.1371/journal.ppat.1010643⟩. ⟨hal-03704136⟩
188 View
12 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More