scholarly journals P-Glycoprotein Inhibitors Differently Affect Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti Proliferation in Bovine Primary Endothelial Cells

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 395
Author(s):  
Camilo Larrazabal ◽  
Liliana M. R. Silva ◽  
Learta Pervizaj-Oruqaj ◽  
Susanne Herold ◽  
Carlos Hermosilla ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cholesterol Metabolism ◽  
Neospora Caninum ◽  
Physiological Role ◽  
Building Blocks ◽  
Besnoitia Besnoiti ◽  
P Glycoprotein ◽  
Pre Treatment

Apicomplexan parasites are obligatory intracellular protozoa. In the case of Toxoplasma gondii, Neospora caninum or Besnoitia besnoiti, to ensure proper tachyzoite production, they need nutrients and cell building blocks. However, apicomplexans are auxotrophic for cholesterol, which is required for membrane biosynthesis. P-glycoprotein (P-gp) is a transmembrane transporter involved in xenobiotic efflux. However, the physiological role of P-gp in cholesterol metabolism is unclear. Here, we analyzed its impact on parasite proliferation in T. gondii-, N. caninum- and B. besnoiti-infected primary endothelial cells by applying different generations of P-gp inhibitors. Host cell treatment with verapamil and valspodar significantly diminished tachyzoite production in all three parasite species, whereas tariquidar treatment affected proliferation only in B. besnoiti. 3D-holotomographic analyses illustrated impaired meront development driven by valspodar treatment being accompanied by swollen parasitophorous vacuoles in the case of T. gondii. Tachyzoite and host cell pre-treatment with valspodar affected infection rates in all parasites. Flow cytometric analyses revealed verapamil treatment to induce neutral lipid accumulation. The absence of a pronounced anti-parasitic impact of tariquidar, which represents here the most selective P-gp inhibitor, suggests that the observed effects of verapamil and valspodar are associated with mechanisms independent of P-gp. Out of the three species tested here, this compound affected only B. besnoiti proliferation and its effect was much milder as compared to verapamil and valspodar.

scholarly journals Importance of serological cross-reactivity amongToxoplasma gondii, Hammondiaspp.,Neosporaspp.,Sarcocystisspp. andBesnoitia besnoiti

Parasitology ◽  
2017 ◽  
Vol 144 (7) ◽  
pp. 851-868 ◽  
Author(s):  
LUÍS F. P. GONDIM ◽  
JOSÉ R. MINEO ◽  
GEREON SCHARES
Keyword(s):  
Toxoplasma Gondii ◽  
Neospora Caninum ◽  
Cross Reactivity ◽  
Besnoitia Besnoiti ◽  
Cross Reactions ◽  
Epidemiological Surveys ◽  
Specific Proteins ◽  
Specific Antigens ◽  
Species Specific

SUMMARYToxoplasma gondii, Neosporaspp.,Sarcocystisspp.,Hammondiaspp. andBesnoitia besnoitiare genetically related cyst-forming coccidia. Serology is frequently used for the identification ofT. gondii, Neosporaspp. andB. besnoiti-exposed individuals. Serologic cross-reactions occur in different tests among animals infected withT. gondiiandH. hammondi,as well as among animals infected byT. gondiiandN. caninum. Infections caused byN. caninumandN. hughesiare almost indistinguishable by serology.Neospora caninum, B. besnoitiandSarcocystisspp. infections in cattle show some degree of serologic cross-reactivity. Antibody cross-reactivity betweenNeosporaspp. andH. heydorni-infected animals is suspected, but not proven to occur. We review serologic cross-reactivity among animals and/or humans infected withT. gondii, Neosporaspp.,Sarcocystisspp.,Hammondiaspp. andB. besnoiti. Emphasis is laid upon antigens and serological methods forN. caninumdiagnosis which were tested for cross-reactivity with related protozoa. Species-specific antigens, as well as stage-specific proteins have been identified in some of these parasites and have promising use for diagnosis and epidemiological surveys.

scholarly journals Toxoplasma gondii Rhoptry Discharge Correlates with Activation of the Early Growth Response 2 Host Cell Transcription Factor

2008 ◽  
Vol 76 (10) ◽  
pp. 4703-4712 ◽  
Author(s):  
Eric D. Phelps ◽  
Kristin R. Sweeney ◽  
Ira J. Blader
Keyword(s):  
Transcription Factor ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Growth Response ◽  
Neospora Caninum ◽  
Early Growth ◽  
Apicomplexan Parasite ◽  
Host Cells ◽  
Early Growth Response ◽  
Cell Extracts

ABSTRACT Toxoplasma gondii is a ubiquitous apicomplexan parasite that can cause severe disease in fetuses and immune-compromised patients. Rhoptries, micronemes, and dense granules, which are secretory organelles unique to Toxoplasma and other apicomplexan parasites, play critical roles in parasite growth and virulence. To understand how these organelles modulate infected host cells, we sought to identify host cell transcription factors triggered by their release. Early growth response 2 (EGR2) is a host cell transcription factor that is rapidly upregulated and activated in Toxoplasma-infected cells but not in cells infected with the closely related apicomplexan parasite Neospora caninum. EGR2 upregulation occurred only when live parasites were in direct contact with the host cell and not from exposure to cell extracts that contain dense granule or micronemal proteins. When microneme-mediated attachment was blocked by pretreating parasites with a calcium chelator, EGR2 expression was significantly reduced. In contrast, when host cells were infected with parasites in the presence of cytochalasin D, which allows rhoptry secretion but prevents parasite invasion, EGR2 was activated. Finally, we demonstrate that Toxoplasma activation of host p38 mitogen-activated protein kinase is necessary but not sufficient for EGR2 activation. Collectively, these data indicate that EGR2 is specifically upregulated by a parasite-derived secreted factor that is most likely a resident rhoptry protein.

Besnoitia besnoiti and Toxoplasma gondii: two apicomplexan strategies to manipulate the host cell centrosome and Golgi apparatus

Parasitology ◽  
2014 ◽  
Vol 141 (11) ◽  
pp. 1436-1454 ◽  
Author(s):  
RITA CARDOSO ◽  
SOFIA NOLASCO ◽  
JOÃO GONÇALVES ◽  
HELDER C. CORTES ◽  
ALEXANDRE LEITÃO ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Golgi Apparatus ◽  
Host Cell ◽  
Parasitophorous Vacuole ◽  
Host Cells ◽  
Besnoitia Besnoiti ◽  
Microtubule Cytoskeleton ◽  
Cytoskeleton Organization ◽  
Evolutionary Paths ◽  
The Impact

SUMMARYBesnoitia besnoiti and Toxoplasma gondii are two closely related parasites that interact with the host cell microtubule cytoskeleton during host cell invasion. Here we studied the relationship between the ability of these parasites to invade and to recruit the host cell centrosome and the Golgi apparatus. We observed that T. gondii recruits the host cell centrosome towards the parasitophorous vacuole (PV), whereas B. besnoiti does not. Notably, both parasites recruit the host Golgi apparatus to the PV but its organization is affected in different ways. We also investigated the impact of depleting and over-expressing the host centrosomal protein TBCCD1, involved in centrosome positioning and Golgi apparatus integrity, on the ability of these parasites to invade and replicate. Toxoplasma gondii replication rate decreases in cells over-expressing TBCCD1 but not in TBCCD1-depleted cells; while for B. besnoiti no differences were found. However, B. besnoiti promotes a reorganization of the Golgi ribbon previously fragmented by TBCCD1 depletion. These results suggest that successful establishment of PVs in the host cell requires modulation of the Golgi apparatus which probably involves modifications in microtubule cytoskeleton organization and dynamics. These differences in how T. gondii and B. besnoiti interact with their host cells may indicate different evolutionary paths.

scholarly journals Species-specific differences in Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti seroprevalence in Namibian wildlife

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Anne Seltmann ◽  
Gereon Schares ◽  
Ortwin H. K. Aschenborn ◽  
Sonja K. Heinrich ◽  
Susanne Thalwitzer ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Neospora Caninum ◽  
Animal Health ◽  
Natural Habitat ◽  
Parasitic Infections ◽  
Besnoitia Besnoiti ◽  
Acinonyx Jubatus ◽  
Apicomplexan Parasites ◽  
Wildlife Species ◽  
African Lions

Abstract Background Knowledge about parasitic infections is crucial information for animal health, particularly of free-ranging species that might come into contact with livestock and humans. Methods We investigated the seroprevalence of three tissue-cyst-forming apicomplexan parasites (Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti) in 506 individuals of 12 wildlife species in Namibia using in-house enzyme linked immunosorbent assays (indirect ELISAs applying purified antigens) for screening and immunoblots as confirmatory tests. We included six species of the suborder Feliformia, four species of the suborder Caniformia and two species of the suborder Ruminantia. For the two species for which we had most samples and life-history information, i.e. cheetahs (Acinonyx jubatus, n = 250) and leopards (Panthera pardus, n = 58), we investigated T. gondii seroprevalence in relation to age class, sex, sociality (solitary, mother-offspring group, independent sibling group, coalition group) and site (natural habitat vs farmland). Results All but one carnivore species (bat-eared fox Otocyon megalotis, n = 4) were seropositive to T. gondii, with a seroprevalence ranging from 52.4% (131/250) in cheetahs to 93.2% (55/59) in African lions (Panthera leo). We also detected antibodies to T. gondii in 10.0% (2/20) of blue wildebeest (Connochaetes taurinus). Adult cheetahs and leopards were more likely to be seropositive to T. gondii than subadult conspecifics, whereas seroprevalence did not vary with sex, sociality and site. Furthermore, we measured antibodies to N. caninum in 15.4% (2/13) of brown hyenas (Hyaena brunnea) and 2.6% (1/39) of black-backed jackals (Canis mesomelas). Antibodies to B. besnoiti were detected in 3.4% (2/59) of African lions and 20.0% (4/20) of blue wildebeest. Conclusions Our results demonstrate that Namibian wildlife species were exposed to apicomplexan parasites at different prevalences, depending on parasite and host species. In addition to serological work, molecular work is also needed to better understand the sylvatic cycle and the clear role of wildlife in the epidemiology of these parasites in southern Africa.

scholarly journals Seroprevalence and Clinical Outcomes of Neospora caninum, Toxoplasma gondii and Besnoitia besnoiti Infections in Water Buffaloes (Bubalus bubalis)

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 532 ◽  
Author(s):  
Lavinia Ciuca ◽  
Giuliano Borriello ◽  
Antonio Bosco ◽  
Luigi D’Andrea ◽  
Giuseppe Cringoli ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Neospora Caninum ◽  
Animal Health ◽  
Bubalus Bubalis ◽  
Clinical Findings ◽  
Besnoitia Besnoiti ◽  
High Exposure ◽  
Water Buffaloes ◽  
Logistic Regression Models ◽  
Parasitic Pathogens

One hundred twenty-four water buffaloes (Bubalus bubalis) originating from 9 farms located in southern Italy were tested to investigate simultaneously, for the first time, the seroprevalence of the protozoa Neospora caninum, Toxoplasma gondii and Besnoitia besnoiti by ELISA tests and to evaluate the clinical findings potentially associated to the presence of these aborting parasitic pathogens. Twenty-five of 124 buffaloes (20.2%) were positive for N. caninum, while 17/124 (13.7%) for T. gondii. No buffalo showed specific antibodies for B. besnoiti. Nineteen of 124 animals (15.3%) were found seropositive for both T. gondii and N. caninum. The univariate statistical analysis showed that the seroprevalence of N. caninum is significantly associated with abortion and presence of retained foetal membranes, while the seroprevalence of T. gondii is significantly associated with an increase of days open. The logistic regression models showed that the co-infection by N. caninum and T. gondii strengthened the abortive effects (OR = 7.330) and showed further negative effects on the parameter embryonic death (OR = 2.607). The outcome revealed herein represents a high exposure of N. caninum and T. gondii in water buffaloes with reproduction disorders that deserves attention for both economic reasons, animal health and welfare.

scholarly journals The structure of a major surface antigen SAG19 from Eimeria tenella unifies the Eimeria SAG family

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nur Zazarina Ramly ◽  
Samuel R. Dix ◽  
Sergey N. Ruzheinikov ◽  
Svetlana E. Sedelnikova ◽  
Patrick J. Baker ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Neospora Caninum ◽  
Sequence Similarity ◽  
Surface Antigens ◽  
Eimeria Tenella ◽  
Besnoitia Besnoiti ◽  
Sequence Comparisons ◽  
Host Interactions ◽  
Apicomplexan Parasites ◽  
Major Surface

AbstractIn infections by apicomplexan parasites including Plasmodium, Toxoplasma gondii, and Eimeria, host interactions are mediated by proteins including families of membrane-anchored cysteine-rich surface antigens (SAGs) and SAG-related sequences (SRS). Eimeria tenella causes caecal coccidiosis in chickens and has a SAG family with over 80 members making up 1% of the proteome. We have solved the structure of a representative E. tenella SAG, EtSAG19, revealing that, despite a low level of sequence similarity, the entire Eimeria SAG family is unified by its three-layer αβα fold which is related to that of the CAP superfamily. Furthermore, sequence comparisons show that the Eimeria SAG fold is conserved in surface antigens of the human coccidial parasite Cyclospora cayetanensis but this fold is unrelated to that of the SAGs/SRS proteins expressed in other apicomplexans including Plasmodium species and the cyst-forming coccidia Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti. However, despite having very different structures, Consurf analysis showed that Eimeria SAG and Toxoplasma SRS families each exhibit marked hotspots of sequence hypervariability that map to their surfaces distal to the membrane anchor. This suggests that the primary and convergent purpose of the different structures is to provide a platform onto which sequence variability can be imposed.

scholarly journals Infection by Toxoplasma gondii Specifically Induces Host c-Myc and the Genes This Pivotal Transcription Factor Regulates

2014 ◽  
Vol 13 (4) ◽  
pp. 483-493 ◽  
Author(s):  
Magdalena Franco ◽  
Anjali J. Shastri ◽  
John C. Boothroyd
Keyword(s):  
Transcription Factor ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Host Response ◽  
Neospora Caninum ◽  
Apicomplexan Parasite ◽  
Intracellular Growth ◽  
Terminal Protein ◽  
Content Type ◽  
Cell Functions

ABSTRACT Toxoplasma gondii infection has previously been described to cause dramatic changes in the host transcriptome by manipulating key regulators, including STATs, NF-κB, and microRNAs. Here, we report that Toxoplasma tachyzoites also mediate rapid and sustained induction of another pivotal regulator of host cell transcription, c-Myc. This induction is seen in cells infected with all three canonical types of Toxoplasma but not the closely related apicomplexan parasite Neospora caninum . Coinfection of cells with both Toxoplasma and Neospora still results in an increase in the level of host c-Myc, showing that c-Myc is actively upregulated by Toxoplasma infection (rather than repressed by Neospora ). We further demonstrate that this upregulation may be mediated through c-Jun N-terminal protein kinase (JNK) and is unlikely to be a nonspecific host response, as heat-killed Toxoplasma parasites do not induce this increase and neither do nonviable parasites inside the host cell. Finally, we show that the induced c-Myc is active and that transcripts dependent on its function are upregulated, as predicted. Hence, c-Myc represents an additional way in which Toxoplasma tachyzoites have evolved to specifically alter host cell functions during intracellular growth.

scholarly journals Histone H2A and Bovine Neutrophil Extracellular Traps Induce Damage of Besnoitia besnoiti-Infected Host Endothelial Cells but Fail to Affect Total Parasite Proliferation

Biology ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 78 ◽  
Author(s):  
Conejeros ◽  
Velásquez ◽  
Grob ◽  
Zhou ◽  
Salecker ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Host Cell ◽  
Cell Damage ◽  
Neutrophil Extracellular Traps ◽  
Host Cells ◽  
Infected Host ◽  
Parasite Development ◽  
Besnoitia Besnoiti ◽  
Extracellular Traps ◽  
Bovine Endothelial Cells

Besnoitia besnoiti tachyzoites infect and develop in bovine endothelial cells in vivo and trigger the release of neutrophil extracellular traps (NETs) from bovine polymorphonuclear neutrophils (PMN). The purpose of this study was to analyze if pure B. besnoiti tachyzoite-triggered NETs would damage endothelial host cells and subsequently influence intracellular development and proliferation of B. besnoiti tachyzoites in primary bovine endothelial cells. For comparison purposes, isolated A23187-induced NETs were also used. Thus, we here evaluated endothelial host cell damage triggered by histone 2A (H2A) and B. besnoiti tachyzoite-induced NET preparations and furthermore estimated the effects of PMN floating over B. besnoiti-infected endothelium under physiological flow conditions on endothelial host cell viability. Overall, all treatments (H2A, B. besnoiti-triggered NETs and floating PMN) induced endothelial cell death of B. besnoiti-infected host cells. However, though host cell damage led to significantly altered intracellular parasite development with respect to parasitophorous vacuole diameter and numbers, the total proliferation of the parasite over time was not significantly affected by these treatments thereby denying any direct effect of NETs on intracellular B. besnoiti replication.

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