scholarly journals Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development

2017 ◽  
Vol 114 (7) ◽  
pp. E1138-E1147 ◽  
Author(s):  
Cláudia Sá e Cunha ◽  
Britta Nyboer ◽  
Kirsten Heiss ◽  
Margarida Sanches-Vaz ◽  
Diana Fontinha ◽  
...  
Keyword(s):  
Parasitophorous Vacuole ◽  
Malaria Prevention ◽  
Rapid Expansion ◽  
Parasite Protein ◽  
Liver Stage ◽  
Apolipoprotein H ◽  
Replication Phase ◽  
Parasite Infections ◽  
Stage Development ◽  
Host Parasite

The first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Hepatic Plasmodium development occurs inside a specialized membranous compartment termed the parasitophorous vacuole (PV). Here, we show that, during the parasite’s hepatic replication, the C-terminal region of the parasitic PV membrane protein exported protein 1 (EXP-1) binds to host Apolipoprotein H (ApoH) and that this molecular interaction plays a pivotal role for successful Plasmodium liver-stage development. Expression of a truncated EXP-1 protein, missing the specific ApoH interaction site, or down-regulation of ApoH expression in either hepatic cells or mouse livers by RNA interference resulted in impaired intrahepatic development. Furthermore, infection of mice with sporozoites expressing a truncated version of EXP-1 resulted in both a significant reduction of liver burden and delayed blood-stage patency, leading to a disease outcome different from that generally induced by infection with wild-type parasites. This study identifies a host–parasite protein interaction during the hepatic stage of infection by Plasmodium parasites. The identification of such vital interactions may hold potential toward the development of novel malaria prevention strategies.

scholarly journals Characterization of the Tubovesicular Network in Plasmodium vivax Liver Stage Hypnozoites and Schizonts

2021 ◽  
Vol 11 ◽  
Author(s):  
Kayla Sylvester ◽  
Steven P. Maher ◽  
Dora Posfai ◽  
Michael K. Tran ◽  
McKenna C. Crawford ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Molecular Mechanisms ◽  
Parasitophorous Vacuole ◽  
Clinical Relapse ◽  
Liver Stage ◽  
Apicomplexan Parasites ◽  
Stage Development ◽  
Host Parasite ◽  
High Resolution Microscopy

Plasmodium is a genus of apicomplexan parasites which replicate in the liver before causing malaria. Plasmodium vivax can also persist in the liver as dormant hypnozoites and cause clinical relapse upon activation, but the molecular mechanisms leading to activation have yet to be discovered. In this study, we use high-resolution microscopy to characterize temporal changes of the P. vivax liver stage tubovesicular network (TVN), a parasitophorous vacuole membrane (PVM)-derived network within the host cytosol. We observe extended membrane clusters, tubules, and TVN-derived vesicles present throughout P. vivax liver stage development. Additionally, we demonstrate an unexpected presence of the TVN in hypnozoites and observe some association of this network to host nuclei. We also reveal that the host water and solute channel aquaporin-3 (AQP3) associates with TVN-derived vesicles and extended membrane clusters. AQP3 has been previously shown to localize to the PVM of P. vivax hypnozoites and liver schizonts but has not yet been shown in association to the TVN. Our results highlight host-parasite interactions occur in both dormant and replicating liver stage P. vivax forms and implicate AQP3 function during this time. Together, these findings enhance our understanding of P. vivax liver stage biology through characterization of the TVN with an emphasis on the presence of this network in dormant hypnozoites.

scholarly journals Hijacking of the host cell Golgi by Plasmodium liver stage parasites

2020 ◽  
Author(s):  
Mariana De Niz ◽  
Gesine Kaiser ◽  
Benoit Zuber ◽  
Won Do Heo ◽  
Volker T. Heussler ◽  
...  
Keyword(s):  
Host Cell ◽  
Parasitophorous Vacuole ◽  
Dominant Negative ◽  
Rab Gtpases ◽  
Cell Organelles ◽  
Liver Stage ◽  
Golgi Fragmentation ◽  
Stage Development ◽  
Golgi Structure ◽  
Dynamic Fluorescence

AbstractThe intracellular lifestyle represents a challenge for the rapidly proliferating liver stage Plasmodium parasite. In order to scavenge host resources, Plasmodium has evolved the ability to target and manipulate host cell organelles. Using dynamic fluorescence-based imaging, we show a direct interplay between the pre-erythrocytic stages of Plasmodium berghei and the host cell Golgi during the entire liver stage development. Liver stage schizonts fragment the host cell Golgi into miniaturized stacks, which increases surface interactions with the parasite’s parasitophorous vacuole membrane. Interference with the host cell Golgi-linked vesicular machinery using specific dominant-negative Arf and Rab GTPases results in developmental arrest and diminished survival of liver stage parasites. Moreover, functional Rab11a is critical for the parasites ability to induce Golgi fragmentation. Altogether, we demonstrate that the structural and functional integrity of the host cell Golgi is necessary for optimal pre-erythrocytic development of P. berghei. The parasite hijacks the hepatocyte’s Golgi structure to optimize its own intracellular development.

scholarly journals Plasmodium falciparum PF10_0164 (ETRAMP10.3) Is an Essential Parasitophorous Vacuole and Exported Protein in Blood Stages

2010 ◽  
Vol 9 (5) ◽  
pp. 784-794 ◽  
Author(s):  
Drew C. MacKellar ◽  
Matthew T. O'Neill ◽  
Ahmed S. I. Aly ◽  
John B. Sacci ◽  
Alan F. Cowman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Parasitophorous Vacuole ◽  
Structural Similarity ◽  
Plasmodium Yoelii ◽  
Parasitophorous Vacuole Membrane ◽  
Liver Stage ◽  
Content Type ◽  
Vacuole Membrane ◽  
Stage Development ◽  
Gene 4

ABSTRACT Upregulated in infectious sporozoites gene 4 (UIS4) encodes a parasitophorous vacuole membrane protein expressed in the sporozoite and liver stages of rodent malaria parasites. Parasites that lack UIS4 arrest in early liver-stage development, and vaccination of mice with uis4 − sporozoites confers sterile protection against challenge with infectious sporozoites. Currently, it remains unclear whether an ortholog of UIS4 is carried in the human malaria parasite Plasmodium falciparum, although the gene PF10_0164 has been identified as a candidate ortholog for UIS4 on the basis of synteny and structural similarity of the encoded protein. We show that PF10_0164 is expressed in sporozoites and blood stages of P. falciparum, where it localizes to the parasitophorous vacuole, and is also exported to the host erythrocyte. PF10_0164 is refractory to disruption in asexual blood stages. Functional complementation was tested in Plasmodium yoelii by replacing the endogenous copy of UIS4 with PF10_0164. PF10_0164 localized to the parasitophorous vacuole membrane of liver stages, but transgenic parasites did not complete liver-stage development in mice. We conclude that PF10_0164 is a parasitophorous vacuole protein that is essential in asexual blood stages and that does not complement P. yoelii UIS4, and it is thus likely not a functional ortholog of UIS4.

scholarly journals The tubovesicular network in Plasmodium vivax liver-stage hypnozoites and schizonts associates with host aquaporin 3

2020 ◽  
Author(s):  
Kayla Sylvester ◽  
Steven P. Maher ◽  
Dora Posfai ◽  
Michael K. Tran ◽  
McKenna C. Crawford ◽  
...  
Keyword(s):  
High Resolution ◽  
Parasitophorous Vacuole ◽  
Parasitophorous Vacuole Membrane ◽  
Liver Stage ◽  
Vacuole Membrane ◽  
Aquaporin 3 ◽  
Host Parasite Interactions ◽  
Host Parasite ◽  
High Resolution Microscopy ◽  
Stage Infection

AbstractThe apicomplexan Plasmodium parasites replicate in the liver before causing malaria. P. vivax can also persist in the liver as dormant hypnozoites and cause relapses upon activation. The host water and solute channel aquaporin-3 (AQP3) has been shown to localize to the parasitophorous vacuole membrane (PVM) of P. vivax hypnozoites and liver schizonts, along with other Plasmodium species and stages. In this study, we use high-resolution microscopy to characterize temporal changes of the tubovesicular network (TVN), a PVM-derived network within the host cytosol, during P. vivax liver-stage infection. We demonstrate an unexpected role for the TVN in hypnozoites and reveal AQP3 associates with TVN-derived vesicles and extended membrane features. We further show AQP3 recruitment to Toxoplasma gondii. Our results highlight dynamic host-parasite interactions that occur in both dormant and replicating liver-stage P. vivax forms and implicate AQP3 function during this time. Together, these findings enhance our understanding of AQP3 in apicomplexan infection.

scholarly journals Association of Plasmodium berghei With the Apical Domain of Hepatocytes Is Necessary for the Parasite's Liver Stage Development

2020 ◽  
Vol 9 ◽  
Author(s):  
Lakshmi Balasubramanian ◽  
Vanessa Zuzarte-Luís ◽  
Tabish Syed ◽  
Debakshi Mullick ◽  
Saptarathi Deb ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Liver Stage ◽  
Apical Domain ◽  
Stage Development

scholarly journals Sequestration of cholesterol within the host late endocytic pathway restricts liver-stage Plasmodium development

2017 ◽  
Vol 28 (6) ◽  
pp. 726-735 ◽  
Author(s):  
Wiebke Petersen ◽  
Werner Stenzel ◽  
Olivier Silvie ◽  
Judith Blanz ◽  
Paul Saftig ◽  
...  
Keyword(s):  
Parasitophorous Vacuole ◽  
Parasite Burden ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Parasite Development ◽  
Liver Stage ◽  
Niemann Pick ◽  
Development Analysis ◽  
Endocytic Compartments

While lysosomes are degradative compartments and one of the defenses against invading pathogens, they are also hubs of metabolic activity. Late endocytic compartments accumulate around Plasmodium berghei liver-stage parasites during development, and whether this is a host defense strategy or active recruitment by the parasites is unknown. In support of the latter hypothesis, we observed that the recruitment of host late endosomes (LEs) and lysosomes is reduced in uis4− parasites, which lack a parasitophorous vacuole membrane protein and arrest during liver-stage development. Analysis of parasite development in host cells deficient for late endosomal or lysosomal proteins revealed that the Niemann–Pick type C (NPC) proteins, which are involved in cholesterol export from LEs, and the lysosome-associated membrane proteins (LAMP) 1 and 2 are important for robust liver-stage P. berghei growth. Using the compound U18666A, which leads to cholesterol sequestration in LEs similar to that seen in NPC- and LAMP-deficient cells, we show that the restriction of parasite growth depends on cholesterol sequestration and that targeting this process can reduce parasite burden in vivo. Taken together, these data reveal that proper LE and lysosome function positively contributes to liver-stage Plasmodium development.

scholarly journals Gene Disruption of Plasmodium falciparum p52 Results in Attenuation of Malaria Liver Stage Development in Cultured Primary Human Hepatocytes

PLoS ONE ◽  
2008 ◽  
Vol 3 (10) ◽  
pp. e3549 ◽  
Author(s):  
Ben C. L. van Schaijk ◽  
Chris J. Janse ◽  
Geert-Jan van Gemert ◽  
Melissa R. van Dijk ◽  
Audrey Gego ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Disruption ◽  
Human Hepatocytes ◽  
Liver Stage ◽  
Primary Human Hepatocytes ◽  
Stage Development

Intestinal Parasite Infections after Extended Use of Chloroquine or Primaquine for Malaria Prevention

1998 ◽  
Vol 84 (3) ◽  
pp. 626 ◽  
Author(s):  
David J. Fryauff ◽  
Purnomo Prodjodipuro ◽  
Hassan Basri ◽  
Trevor R. Jones ◽  
Eric Mouzin ◽  
...  
Keyword(s):  
Intestinal Parasite ◽  
Malaria Prevention ◽  
Parasite Infections

scholarly journals Plasmodium vivax Liver Stage Development and Hypnozoite Persistence in Human Liver-Chimeric Mice

2015 ◽  
Vol 17 (4) ◽  
pp. 536 ◽  
Author(s):  
Sebastian A. Mikolajczak ◽  
Ashley M. Vaughan ◽  
Niwat Kangwanrangsan ◽  
Wanlapa Roobsoong ◽  
Matthew Fishbaugher ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Human Liver ◽  
Chimeric Mice ◽  
Liver Stage ◽  
Stage Development

Eimeria canadensis (Protozoa, Sporozoea): ultrastructure of the host–parasite interface during development of first-generation schizonts in vitro

1980 ◽  
Vol 58 (11) ◽  
pp. 2018-2025 ◽  
Author(s):  
Bodo E. G. Mueller
Keyword(s):  
Host Cell ◽  
Parasitophorous Vacuole ◽  
Eimeria Species ◽  
Outer Zone ◽  
Ultrastructural Observation ◽  
Cell Cytoplasm ◽  
Cell Organelles ◽  
Host Cell Cytoplasm ◽  
Host Parasite

Eimeria canadensis sporozoites were inoculated into monolayer cultures of Madin–Darby bovine kidney and primary bovine embryonic kidney cells. Sporozoites retained their shape for at least 9 days. At that time, the nucleus was enlarged and contained a prominent nucleolus, and amylopectin granules were no longer apparent. The width of the parasitophorous vacuole (pv) between host cell cytoplasm and parasite pellicle widened during transformation of sporozoites into multinucleate schizonts. Areas of altered host cell cytoplasm immediately adjacent to the pv membrane increased in size and became confluent, resulting in the formation of two distinct layers of cytoplasm. The outer zone contained the host cell nucleus, mitochondria, Golgi stacks, and ER, whereas the inner layer appeared granular and was void of all cell organelles except structures resembling ribosomes. Microfilaments were abundant at the border between inner and outer zone. In the most advanced stages observed, host cell organelles persisted only in the perinuclear region. The remaining, attenuated cytoplasm resembled the former inner zone.The novel ultrastructural observation of a bilayered cytoplasm of cells harbouring E. canadensis schizonts is compared with light microscope reports of similar effects caused by other Eimeria species of ruminants and with electron microscope findings of altered intestinal and abomasal cells of sheep harbouring "globidial" schizonts.

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