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The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites

Invasion of host cells by apicomplexan parasites such as Toxoplasma and Plasmodium spp requires the sequential secretion of the parasite apical organelles, the micronemes and the rhoptries. The claudin-like apicomplexan microneme protein (CLAMP) is a conserved protein that plays an essential role du...

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Autores principales: Loubens, Manon, Marinach, Carine, Paquereau, Clara-Eva, Hamada, Soumia, Hoareau-Coudert, Bénédicte, Akbar, David, Franetich, Jean-François, Silvie, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047546/
https://www.ncbi.nlm.nih.gov/pubmed/36928686
http://dx.doi.org/10.1371/journal.ppat.1011261
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author Loubens, Manon
Marinach, Carine
Paquereau, Clara-Eva
Hamada, Soumia
Hoareau-Coudert, Bénédicte
Akbar, David
Franetich, Jean-François
Silvie, Olivier
author_facet Loubens, Manon
Marinach, Carine
Paquereau, Clara-Eva
Hamada, Soumia
Hoareau-Coudert, Bénédicte
Akbar, David
Franetich, Jean-François
Silvie, Olivier
author_sort Loubens, Manon
collection PubMed
description Invasion of host cells by apicomplexan parasites such as Toxoplasma and Plasmodium spp requires the sequential secretion of the parasite apical organelles, the micronemes and the rhoptries. The claudin-like apicomplexan microneme protein (CLAMP) is a conserved protein that plays an essential role during invasion by Toxoplasma gondii tachyzoites and in Plasmodium falciparum asexual blood stages. CLAMP is also expressed in Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, but its role in this stage is still unknown. CLAMP is essential for Plasmodium blood stage growth and is refractory to conventional gene deletion. To circumvent this obstacle and study the function of CLAMP in sporozoites, we used a conditional genome editing strategy based on the dimerisable Cre recombinase in the rodent malaria model parasite P. berghei. We successfully deleted clamp gene in P. berghei transmission stages and analyzed the functional consequences on sporozoite infectivity. In mosquitoes, sporozoite development and egress from oocysts was not affected in conditional mutants. However, invasion of the mosquito salivary glands was dramatically reduced upon deletion of clamp gene. In addition, CLAMP-deficient sporozoites were impaired in cell traversal and productive invasion of mammalian hepatocytes. This severe phenotype was associated with major defects in gliding motility and with reduced shedding of the sporozoite adhesin TRAP. Expansion microscopy revealed partial colocalization of CLAMP and TRAP in a subset of micronemes, and a distinct accumulation of CLAMP at the apical tip of sporozoites. Collectively, these results demonstrate that CLAMP is essential across invasive stages of the malaria parasite, and support a role of the protein upstream of host cell invasion, possibly by regulating the secretion or function of adhesins in Plasmodium sporozoites.
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spelling pubmed-100475462023-03-29 The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites Loubens, Manon Marinach, Carine Paquereau, Clara-Eva Hamada, Soumia Hoareau-Coudert, Bénédicte Akbar, David Franetich, Jean-François Silvie, Olivier PLoS Pathog Research Article Invasion of host cells by apicomplexan parasites such as Toxoplasma and Plasmodium spp requires the sequential secretion of the parasite apical organelles, the micronemes and the rhoptries. The claudin-like apicomplexan microneme protein (CLAMP) is a conserved protein that plays an essential role during invasion by Toxoplasma gondii tachyzoites and in Plasmodium falciparum asexual blood stages. CLAMP is also expressed in Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, but its role in this stage is still unknown. CLAMP is essential for Plasmodium blood stage growth and is refractory to conventional gene deletion. To circumvent this obstacle and study the function of CLAMP in sporozoites, we used a conditional genome editing strategy based on the dimerisable Cre recombinase in the rodent malaria model parasite P. berghei. We successfully deleted clamp gene in P. berghei transmission stages and analyzed the functional consequences on sporozoite infectivity. In mosquitoes, sporozoite development and egress from oocysts was not affected in conditional mutants. However, invasion of the mosquito salivary glands was dramatically reduced upon deletion of clamp gene. In addition, CLAMP-deficient sporozoites were impaired in cell traversal and productive invasion of mammalian hepatocytes. This severe phenotype was associated with major defects in gliding motility and with reduced shedding of the sporozoite adhesin TRAP. Expansion microscopy revealed partial colocalization of CLAMP and TRAP in a subset of micronemes, and a distinct accumulation of CLAMP at the apical tip of sporozoites. Collectively, these results demonstrate that CLAMP is essential across invasive stages of the malaria parasite, and support a role of the protein upstream of host cell invasion, possibly by regulating the secretion or function of adhesins in Plasmodium sporozoites. Public Library of Science 2023-03-16 /pmc/articles/PMC10047546/ /pubmed/36928686 http://dx.doi.org/10.1371/journal.ppat.1011261 Text en © 2023 Loubens 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
Loubens, Manon
Marinach, Carine
Paquereau, Clara-Eva
Hamada, Soumia
Hoareau-Coudert, Bénédicte
Akbar, David
Franetich, Jean-François
Silvie, Olivier
The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites
title The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites
title_full The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites
title_fullStr The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites
title_full_unstemmed The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites
title_short The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites
title_sort claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of plasmodium sporozoites
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047546/
https://www.ncbi.nlm.nih.gov/pubmed/36928686
http://dx.doi.org/10.1371/journal.ppat.1011261
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