Host cell invasion by apicomplexan parasites: the junction conundrum

No abstract available

Protein Phosphatase 2C of Toxoplasma Gondii Interacts with Human SSRP1 and Negatively Regulates Cell Apoptosis

International audienceBiographical notes of the first authors: GAO Xue Juan, female, born in 1980, PhD, assistant researcher, majoring in protein-protein interaction and signaling pathways; FENG Jun Xia, female, born in 1989, majoring in pathogenic molecular mechanism of pathogenic microorganisms. Abstract Objective The protozoan Toxoplasma gondii expresses large amounts of a 37 kDa Type 2C serine-threonine phosphatase, the so-called TgPP2C which has been suggested to contribute to parasite growth regulation. Ectopic expression in mammalian cells also indicated that the enzyme could regulate growth and survival. In this study, we aimed to investigate the interaction of TgPP2C with human SSRP1 (structure-specific recognition protein 1) and the effects of TgPP2C on cell viability. Methods The yeast two hybrid system, His-tag pull-down and co-immunoprecipitation assays were used to confirm the interaction of TgPP2C with SSRP1 and determine the binding domain on SSRP1. The evaluation of cell apoptosis was performed using cleaved caspase-3 antibody and Annexin-V/PI kit combined with flow cytometry. Results We identified human SSRP1 as an interacting partner of TgPP2C. The C-terminal region of SSRP1 including the amino acids 471 to 538 was specifically mapped as the region responsible for interaction with TgPP2C. The overexpression of TgPP2C down-regulated cell apoptosis and negatively regulated apoptosis induced by DRB, casein kinase II (CKII) inhibitor, through enhanced interaction with SSRP1. Conclusion TgPP2C may be a parasitic factor capable of promoting cell survival through interaction with the host protein SSRP1, thereby creating a favorable environment for parasite growth

Étude de vingt-cinq foyers récents de botulisme animal

Prévot A. R., Huet M., Tardieux P. Étude de vingt-cinq foyers récents de botulisme animal. In: Bulletin de l'Académie Vétérinaire de France tome 103 n°9, 1950. pp. 481-487

BMC Biology BMC Biology The toxoplasma-host cell junction is anchored to the cell cortex to sustain parasite invasive force

International audienceBackgroundThe public health threats imposed by toxoplasmosis worldwide and by malaria in sub-Saharan countries are directly associated with the capacity of their closely related causative agents Toxoplasma and Plasmodium, respectively to colonize and expand inside host cells. Therefore, deciphering how these two Apicomplexan protozoan parasites access their hosting cells has been highlighted as a high priority research with the relevant perspective of designing anti-invasive molecules to prevent diseases. Central to the mechanistic base of invasion for both genera is mechanical force, which is thought to be applied by the parasite at the interface between the two cells following assembly of a unique cell junction but this model lacks direct evidence and has been challenged by recent genetic and cell biology studies. In this work, using parasites expressing the fluorescent core component of this junction, we analyse characteristic features of the kinematics of penetration of more than 1000 invasion events.ResultsThe majority of invasion events occur with a typical forward rotational progression of the parasite through a static junction into a vacuole formed from the invaginating host cell plasma membrane, in which the parasite subsequently replicates. However, if parasites encounter resistance and if the junction is not strongly anchored to the host cell cortex, as when parasites do not secrete the toxofilin protein and therefore are unable to locally remodel the cortical actin cytoskeleton, the junction is capped backwards and travels retrogradely with the host cell membrane along the parasite surface as it is enclosed within a functional vacuole. Kinetic measurements of the invasive trajectories strongly support a similar parasite driven force in both static and capped junctions, both of which lead to successful invasion. However about 20% of toxofilin mutants fail to enter and eventually disengage from the host cell membrane while the secreted RON2 molecules are capped at the posterior pole before being cleaved and released in the medium. By contrast in cells characterized by low cortex tension and high cortical actin dynamics, junction capping and entry failure are drastically reduced.ConclusionThis kinematic analysis of pre-invasive and invasive T. gondii tachyzoite behaviors newly highlights that to invade cells, parasites need to engage their motor with the junction molecular complex where force is efficiently applied only upon proper anchorage to the host cell membrane and cortex

Apicomplexan F-actin is required for efficient nuclear entry during host cell invasion

The obligate intracellular parasites Toxoplasma gondii and Plasmodium spp. invade host cells by injecting a protein complex into the membrane of the targeted cell that bridges the two cells through the assembly of a ring‐like junction. This circular junction stretches while the parasites apply a traction force to pass through, a step that typically concurs with transient constriction of the parasite body. Here we analyse F‐actin dynamics during host cell invasion. Super‐resolution microscopy and real‐time imaging highlighted an F‐actin pool at the apex of pre‐invading parasite, an F‐actin ring at the junction area during invasion but also networks of perinuclear and posteriorly localised F‐actin. Mutant parasites with dysfunctional acto‐myosin showed significant decrease of junctional and perinuclear F‐actin and are coincidently affected in nuclear passage through the junction. We propose that the F‐actin machinery eases nuclear passage by stabilising the junction and pushing the nucleus through the constriction. Our analysis suggests that the junction opposes resistance to the passage of the parasite's nucleus and provides the first evidence for a dual contribution of actin‐forces during host cell invasion by apicomplexan parasites

Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion

Trypanosoma cruzi takes advantage of a sphingomyelinase-dependent plasma membrane repair pathway to gain access to host cells

Systemic arterial hypertension and hospital admissions: improving care in primary care / Hipertensão arterial sistémica e internamentos hospitalares: melhorar os cuidados nos cuidados primários

BACKGROUND: Systemic Arterial Hypertension is a chronic disease that affects the global population and can cause serious harm when not controlled. The prevalence is high and it is one of the conditions that most leads people to death. Therefore, multiprofessional care ensures a better integrality of care and avoids high direct and indirect costs. OBJECTIVE: Describe the context of hospital admissions for Systemic Arterial Hypertension and its consequences for the brazilian national health system. MATERIAL AND METHODS: Descriptive epidemiological study, which used public domain data of the authorization of hospital admissions for hypertension, available in the Hospital Information System of the Brazilian regions, in the period from 2014 to 2020. RESULTS: Were reported, 403,181 hospitalizations for Systemic Arterial Hypertension with an annual mean of 57,597 (?=12,319.9). The North east region (?=39.3, ?=9.0 per 100,000 inhabitants, significant temporal decrease) and North region (?=37.3, ?=8.9 per 100,000 inhabitants, significant temporal decrease) expressed the highest coefficients. Stood out the female population (?=58.5%, ?=1.01%, significant temporal decrease), the elderly (?=56.7%, ?=0.79%, stable) and brown people (?=39.1%, ?=1.2%, stable). The national annual average costs are close to $3.6 million (?=736.7 thousand). CONCLUSION: Improving the actions of Primary Health and knowing the consequences can support the planning and implementation of actions, impact the costs to the health system, as well as ensure that other levels of care perform the respective care, avoiding worsening of the clinical Picture

Vital role for the Plasmodium actin capping protein (CP) beta-subunit in motility of malaria sporozoites

Successful malaria transmission from the mosquito vector to the mammalian host depends crucially on active sporozoite motility. Sporozoite locomotion and host cell invasion are driven by the parasite's own actin/myosin motor. A unique feature of this motor machinery is the presence of very short subpellicular actin filaments. Therefore, F-actin stabilizing proteins likely play a central role in parasite locomotion. Here, we investigated the role of the Plasmodium berghei actin capping protein (PbCP), an orthologue of the heterodimeric regulator of filament barbed end growth, by reverse genetics. Parasites containing a deletion of the CP beta-subunit developed normally during the pathogenic erythrocytic cycle. However, due to reduced ookinete motility, mutant parasites form fewer oocysts and sporozoites in the Anopheles vector. These sporozoites display a vital deficiency in forward gliding motility and fail to colonize the mosquito salivary glands, resulting in complete attenuation of life cycle progression. Together, our results show that the CP beta-subunit exerts an essential role in the insect vector before malaria transmission to the mammalian host. The vital role is restricted to fast locomotion, as displayed by Plasmodium sporozoites