Malaria parasite LIMP protein regulates sporozoite gliding motility and infectivity in mosquito and mammalian hosts

Santos, Jorge M.; Egarter, Saskia; Zuzarte‐Luís, Vanessa; Kumar, Hirdesh; Moreau, Catherine; Kehrer, Jessica; Pinto, Andreia; Costa, Mário da; Franke-Fayard, Blandine; Janse, Chris J.; Frischknecht, Friedrich; Mair, Gunnar R.

doi:10.7554/elife.24109

Cited by 36 publications

(33 citation statements)

References 102 publications

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“…This suggests that SEC13 might not localize to NPCs or only to a subset. Furthermore, the appearance of a second spot in salivary gland derived sporozoites hints at a specific function, possibly in secretion, as these forms need to migrate rapidly, which necessitate the secretion of different proteins 35 , 38 , 39 . However, in the absence of a viable mutant this remains speculation.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Pore Complex Components in the Malaria Parasite Plasmodium berghei

Kehrer

Kuss

Andrés-Pons

et al. 2018

Sci Rep

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The nuclear pore complex (NPC) is a large macromolecular assembly of around 30 different proteins, so-called nucleoporins (Nups). Embedded in the nuclear envelope the NPC mediates bi-directional exchange between the cytoplasm and the nucleus and plays a role in transcriptional regulation that is poorly understood. NPCs display modular arrangements with an overall structure that is generally conserved among many eukaryotic phyla. However, Nups of yeast or human origin show little primary sequence conservation with those from early-branching protozoans leaving those of the malaria parasite unrecognized. Here we have combined bioinformatic and genetic methods to identify and spatially characterize Nup components in the rodent infecting parasite Plasmodium berghei and identified orthologs from the human malaria parasite P. falciparum, as well as the related apicomplexan parasite Toxoplasma gondii. For the first time we show the localization of selected Nups throughout the P. berghei life cycle. Largely restricted to apicomplexans we identify an extended C-terminal poly-proline extension in SEC13 that is essential for parasite survival and provide high-resolution images of Plasmodium NPCs obtained by cryo electron tomography. Our data provide the basis for full characterization of NPCs in malaria parasites, early branching unicellular eukaryotes with significant impact on human health.

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Section: Discussionmentioning

confidence: 99%

Nuclear Pore Complex Components in the Malaria Parasite Plasmodium berghei

Kehrer

Kuss

Andrés-Pons

et al. 2018

Sci Rep

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“…Sporozoite motility was shown to be critical for invasion of salivary glands by targeted gene disruption of TRAP (Ejigiri et al, 2012;Sultan et al, 1997), TREP/S6/UOS3 (Combe, Moreira, et al, 2009;Mikolajczak et al, 2008;Steinbuechel & Matuschewski, 2009), LIMP (Santos et al, 2017), ICP (Boysen & Matuschewski, 2013), actin capping protein (CP, Ganter, Schüler, & Matuschewski, 2009), and plasmepsin VIII (Mastan, Narwal, Dey, Kumar, & Mishra, 2017). Therefore, we examined the sporozoite motility of P msp9 -RON2 haemolymph sporozoites in vitro.…”

Section: Ron2 Plays An Important Role In Sporozoite Invasion Of Salmentioning

confidence: 99%

Rhoptry neck protein 2 expressed in Plasmodium sporozoites plays a crucial role during invasion of mosquito salivary glands

Ishino

Murata

Tokunaga

et al. 2018

Cellular Microbiology

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Malaria parasite transmission to humans is initiated by the inoculation of Plasmodium sporozoites into the skin by mosquitoes. Sporozoites develop within mosquito midgut oocysts, first invade the salivary glands of mosquitoes, and finally infect hepatocytes in mammals. The apical structure of sporozoites is conserved with the infective forms of other apicomplexan parasites that have secretory organelles, such as rhoptries and micronemes. Because some rhoptry proteins are crucial for Plasmodium merozoite infection of erythrocytes, we examined the roles of rhoptry proteins in sporozoites. Here, we demonstrate that rhoptry neck protein 2 (RON2) is also localized to rhoptries in sporozoites. To elucidate RON2 function in sporozoites, we applied a promoter swapping strategy to restrict ron2 transcription to the intraerythrocytic stage in the rodent malaria parasite, Plasmodium berghei. Ron2 knockdown sporozoites were severely impaired in their ability to invade salivary glands, via decreasing the attachment capacity to the substrate. This is the first rhoptry protein demonstrated to be involved in salivary gland invasion. In addition, ron2 knockdown sporozoites showed less infectivity to hepatocytes, possibly due to decreased attachment/gliding ability, indicating that parts of the parasite invasion machinery are conserved, but their contribution might differ among infective forms. Our sporozoite stage‐specific knockdown system will help to facilitate understanding the comprehensive molecular mechanisms of parasite invasion of target cells.

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“…Highly conserved in Plasmodium parasites and related apicomplexans, deletion of LIMP in P. berghei severely impaired gliding motility with large numbers of completely immotile parasites and a corresponding 10-fold reduction in salivary gland invasion (Santos et al, 2017).…”

Section: Limpmentioning

confidence: 99%

The Sporozoite's Journey Through the Mosquito: A Critical Examination of Host and Parasite Factors Required for Salivary Gland Invasion

Kojin

Adelman

2019

Front. Ecol. Evol.

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Although much progress has been made in the fight against malaria, the number of people that contract this disease due to the bite of an Anopheline mosquito remains unacceptably high. A better understanding of the relationship between the Plasmodium parasite and its vector is of extreme importance and may allow for the development of new tools to fight the disease. In particular, new genome editing techniques may allow the modification or removal of factors critical for parasite traversal of the vector mosquito. In this review, we aim to highlight what is known about important molecules encoded by the mosquito or parasite involved in this close interaction, focused on a specific window of the parasite life cycle inside the mosquito: from egress and release of the sporozoites from the oocyst into the hemolymph, until salivary gland penetration. While sophisticated molecular tools have already helped to understand aspects of parasite-mosquito interactions, our understanding of this brief period is still limited. Here, we discuss the evidence surrounding essential parasite and mosquito factors relating to sporozoite invasion of the salivary glands, and emphasize the areas where the lack of information is limiting the advance of strategies to manipulate the mosquito in order to block the transmission of malaria parasites.

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Malaria parasite LIMP protein regulates sporozoite gliding motility and infectivity in mosquito and mammalian hosts

Cited by 36 publications

References 102 publications

Nuclear Pore Complex Components in the Malaria Parasite Plasmodium berghei

Nuclear Pore Complex Components in the Malaria Parasite Plasmodium berghei

Rhoptry neck protein 2 expressed in Plasmodium sporozoites plays a crucial role during invasion of mosquito salivary glands

The Sporozoite's Journey Through the Mosquito: A Critical Examination of Host and Parasite Factors Required for Salivary Gland Invasion

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