Plasmodium sporozoites require the protein B9 to invade hepatocytes

Fernandes, Priyanka; Loubens, Manon; Marinach, Carine; Coppée, Romain; Baron, Ludivine; Grand, Morgane; Andre, Thanh-Phuc; Hamada, Soumia; Langlois, Anne-Claire; Briquet, Sylvie; Bun, Philippe; Silvie, Olivier

doi:10.1016/j.isci.2023.106056

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“…Whether CLAMP controls the secretion of other microneme proteins in Plasmodium sporozoites also deserves further investigation. In this regard, our U-ExM data showing partial co-distribution of CLAMP and TRAP, but not AMA1, support the existence of distinct microneme populations in Plasmodium sporozoites, with possibly distinct trafficking and/or signalling pathways controlling microneme exocytosis [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 68%

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

et al. 2023

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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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Section: Discussionmentioning

confidence: 68%