ArticlePLoS pathogens2022
The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 49 citations in OpenAlex.
- Identification of two genomic cryptotypes of Plasmodium malariae in Africa.PLoS neglected tropical diseases · 2026Article
- High-resolution proteomics unveils salivary gland disruption and saliva-hemolymph protein exchange in Plasmodium-infected mosquitoes.Nature communications · 2025Article
- Secretome and Transcriptome Analyses Reveal New Potential Virulence Factors duringJournal of proteome research · 2025Article
- Understanding the traits underlying vaccine-driven virulence evolution in malaria parasites.BMC biology · 2025Article
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- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- The Plasmodium GRASP Homolog Modulates Liver Stage Development, Subsequent Blood Infection and Virulence in Mice.Molecular microbiology · 2025Article
- A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade.Cell reports. Medicine · 2025Article
- Constitutive expression of Cas9 and rapamycin-inducible Cre recombinase facilitates conditional genome editing in Plasmodium berghei.Scientific reports · 2025Article
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Identification of a novel rhoptry protein expressed predominantly inFrontiers in cellular and infection microbiology · 2025Article
- Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages.Nature communications · 2024Article
- The Plasmodium circumsporozoite protein.Trends in parasitology · 2024Review
- Eimeria: Navigating complex intestinal ecosystems.PLoS pathogens · 2024Review
- Identification and molecular characterization of a novel Babesia orientalis rhoptry neck protein 4 (BoRON4).Parasitology research · 2024Article
- A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites.Nature communications · 2024Article
- Vaccines and monoclonal antibodies: new tools for malaria control.Clinical microbiology reviews · 2024Review
- A screen for Plasmodium falciparum sporozoite surface protein binding to human hepatocyte surface receptors identifies novel host-pathogen interactions.Malaria journal · 2024Article
- State-of-the-art Review on the Antiparasitic Activity of Benzimidazolebased Derivatives: Facing Malaria, Leishmaniasis, and Trypanosomiasis.Current medicinal chemistry · 2024Review
- Structure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies.Nature communications · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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