Search Results (722)

Resistance formation and considerable toxicities limit the application of currently available antiparasitic drugs. Thus, new drug candidates are required. Piperlongumine-based cinnamides are promising antiparasitic compounds. In this study, new synthetic cinnamide derivatives with variable halogen substituents (F, Cl, and Br) were prepared and analyzed. They were tested for activity against Toxoplasma gondii and Leishmania major parasites. Considerable activities against T. gondii parasites were observed for certain chloro- and bromo-substituted cinnamides (IC₅₀ = 1.88–2.72 µM), while activities against L. major were less pronounced. Structure–activity relationships were investigated, which revealed notable relations of anti-toxoplasmal activity with the nature of the applied halogen substituents and a preference for chloro- and bromo-substituents in active compounds. In contrast to piperlongumine, the new active compounds have no methoxy substituents anymore and appear to be suitable for advanced antiparasitic studies. Successful docking of selected derivatives into the colchicine binding site of tubulin provided a strong hint at a possible mode of action for these cinnamides (S-scores of −6.075 and −5.993 kcal/mol). In addition, considerable drug-like properties were determined by ADME-T calculations. Thus, in conclusion, new halo-substituted cinnamides with promising activity against Toxoplasma gondii were identified. The selectivity for Toxoplasma parasites can lead to better drugs for the therapy of toxoplasmosis. Full article

Objective: This study aimed to evaluate the association between T. gondii genotypes (types I, II, III) and cases of spontaneous abortion in humans. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Databases (PubMed, Scopus, Web of Science, EMBASE, and ScienceDirect) were searched for studies published in the last 10 years. Observational studies evaluating T. gondii genotypes in abortion cases were included. Results: Eight cross-sectional studies were included. A pooled positivity proportion for T. gondii of approximately 20% was observed among abortion cases, with substantial heterogeneity (I² > 90%). Genotype distribution varied across studies, with types I and III being the most frequently reported. Conclusions: Available evidence suggests a possible association between T. gondii infection and spontaneous abortion; however, the role of specific genotypes remains uncertain due to limited and heterogeneous data. More multicenter studies are needed to robustly address the issue. Full article

Toxoplasma gondii (T. gondi) is a widespread zoonotic parasite that poses a significant threat to global public health, yet effective therapeutic options remain limited. In this study, we found that the flavonoid compound myricetin (MYR) can significantly inhibit the proliferation of T. gondii. This effect is associated with the inhibition of dihydroorotase (TgDHO) activity in the de novo pyrimidine biosynthesis pathway, and this inhibition can be partially reversed by exogenous supplementation with uracil. Further studies revealed that MYR treatment can induce cell cycle arrest in tachyzoites and impair bradyzoite proliferation, concurrently disrupting the UDP-GlcNAc glycosylation of the cyst wall. In mouse models, MYR demonstrated significant efficacy, achieving an 80% survival rate in acute infection and inducing morphological abnormalities in intracerebral cysts during chronic infection. Collectively, these findings elucidate the anti-Toxoplasma activity and multifaceted mechanisms of MYR, providing valuable insights for developing novel therapeutics against toxoplasmosis. Full article

Toxoplasma gondii is an obligate intracellular parasite that infects virtually all warm-blooded animals, progressing through acute and chronic stages. The Akt/mTOR signaling axis plays critical roles in cell survival, proliferation, and metabolism, making it a key target for intracellular pathogens. This study investigated how T. gondii infection modulates this pathway during both infections. Outbred CD-1 mice were infected intraperitoneally with the virulent GT1 strain of T. gondii. Mice for acute studies were sacrificed five days post-infection, while those for chronic studies were treated with sulfadiazine and sacrificed five months post-infection. Phosphoprotein expression of eight Akt/mTOR pathway components was measured in liver tissues using a multiplexed bead-based immunoassay. Acute T. gondii infection caused broad suppression of Akt/mTOR signaling, with 6 of 8 markers significantly downregulated, including pS6RP^Ser235/236, pAKT^S473, pBAD^Ser136, pIRS1^S636/639, pPTEN^Ser380, and pGSK-3α/β^Ser21/9. In contrast, chronic infection related to cyst burden selectively activates specific nodes of the pathway, including pBAD^Ser136, pmTOR^Ser2448, and pGSK-3α/β^Ser21/9. Infection induced strong correlations between inter-components, which reflect coherent and coordinated pathway-level reprogramming rather than random perturbation. These findings show that acute and chronic T. gondii infections have opposing effects on host Akt/mTOR signaling for their own benefit, which may present new therapeutic targets. Full article

Toxoplasma gondii and Neospora caninum are apicomplexan parasites infecting cattle, with implications for public health and livestock productivity, respectively. Since effective vaccines against these parasites are not currently available, identifying epidemiological factors associated with infection is important for improving control strategies. This study aimed to estimate the seroprevalence of both parasites and to identify factors associated with seropositivity in intensive dairy cattle in central Chile. A cross-sectional study was conducted using serum samples from 567 cattle, analyzed by ELISA. Epidemiological data were collected through semi-structured surveys, and associations with seropositivity were evaluated using multivariable logistic regression models, including mixed-effects models to account for farm-level clustering. Seroprevalence was 7.6% for T. gondii and 22.4% for N. caninum. For T. gondii, factors associated with seropositivity included older age categories (OR = 7.09; 11.25) and the presence of dogs in pens (OR = 6.07). For N. caninum, straw bedding use (OR = 5.13) and cat presence (OR = 6.32) were associated with higher odds of seropositivity. An additional association with lower N. caninum seropositivity was observed for BCG vaccination (OR = 0.24). These findings provide updated epidemiological data for dairy cattle in Chile. The association observed with BCG vaccination should be interpreted cautiously, as the study design does not permit causal inference. Full article

Toxoplasma gondii is an obligate intracellular parasite of the phylum Apicomplexa and the causative agent of toxoplasmosis, a disease with a worldwide distribution that causes serious consequences in immunocompromised patients and during pregnancy. Current pharmacological treatments have significant limitations, including their toxicity, lack of efficacy against the chronic phase of the parasite, and low selectivity, highlighting the need to develop new therapeutic targets. One of the most promising targets is the fatty acid synthesis pathway II (FASII), a metabolic pathway located in the parasite’s apicoplast and absent in mammalian hosts. This review synthesizes the available evidence on FASII pathway inhibitors described to date, as well as their potential impact on the viability and development of T. gondii. Overall, the reviewed studies support the FASII pathway as an attractive therapeutic target for the development of more selective and effective treatments against toxoplasmosis. Full article

Background/Objectives: Toxoplasmosis is a globally distributed parasitic zoonosis caused by Toxoplasma gondii (Apicomplexa, Sarcocystidae), an obligate intracellular protozoan with an indirect life cycle in which domestic cats and wild felids serve as definitive hosts, whereas humans and a broad range of domestic and wild animals act as intermediate hosts. The objective of the study was to document the seroprevalence of anti-Toxoplasma gondii antibodies in professionals and students of Veterinary Medicine in Aguascalientes, Mexico. Methods: The study included 153 clinically healthy individuals from two population segments: Veterinarians (70) and Veterinary Medicine Students (83). Serum samples were analyzed using a commercial ELISA test to determine the presence of T. gondii-specific IgG. A questionnaire was applied to collect sociodemographic information and information about contact with cats. Results: The overall prevalence of anti-T. gondii antibodies in the study population was 7.8% (12/153; CI 95% 4.3–13.6). In the group of Veterinarians, the seroprevalence was 11.4% (8/70; CI 95% 5.4–21.8), while in the group of students it was 4.8% (4/83; CI 95% 1.5–12.5), with no differences observed between them (p = 0.22). Association was found with those who consume raw/undercooked meat (p = 0.002). Conclusions: In this cross-sectional sample of veterinary professionals and students in Aguascalientes, anti-T. gondii IgG seroprevalence was 7.8%, with no statistically significant difference between occupational groups. Consumption of raw or undercooked meat was the only exposure significantly associated with seropositivity. Full article

Toxoplasmosis, caused by the obligate intracellular parasite T. gondii, is one of the most prevalent parasitic infections worldwide, affecting approximately one-third of the global population. Despite decades of intensive research, no effective human vaccine exists. The only commercially available vaccine, Toxovax, is restricted to veterinary use in sheep and is unsuitable for human application due to safety concerns. Beyond summarizing the literature, this review offers a critical appraisal of why translation has stalled and where the field should focus next. Live-attenuated vaccines remain the most immunogenic in preclinical models but face significant translational barriers for human use. Key antigenic targets include surface antigens (SAG), dense granule antigens (GRA), rhoptry proteins (ROP), and microneme proteins (MIC). Protective immunity relies critically on Th1-type immune responses characterized by interferon-gamma production. Major obstacles include the parasite’s complex life cycle, strain diversity, and difficulty achieving sterile immunity. Subunit and mRNA-based platforms offer more favorable safety profiles and established clinical precedents, representing the most viable pathway toward a human vaccine. Recent advances in CRISPR/Cas9 gene editing and emerging mRNA vaccine platforms offer promising new directions. This review advances the field in three ways. (i) It prioritizes mRNA and adjuvanted subunit formulations targeting multistage conserved antigens as the most realistic near-term human candidates. (ii) It identifies the limited targeting of bradyzoite-stage biology as a principal, under-addressed gap. (iii) It argues that future development must be differentiated into three complementary One Health goals—prevention of congenital disease in humans, reduction in tissue-cyst burden in livestock, and interruption of environmental transmission by vaccinating cats. In practice, a veterinary-first deployment strategy is the most immediate and impactful pathway to reducing the human and zoonotic burden of toxoplasmosis. Full article

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis, posing a significant threat to human health and livestock production worldwide. Although monovalent DNA or mRNA vaccines often confer only partial protection, whether these platforms can be effectively integrated into a heterologous prime–boost regimen against T. gondii remains to be fully elucidated. Here, we constructed GRA35-encoding DNA and mRNA vaccines and evaluated their immunogenicity and protective efficacy, administered either alone or in heterologous prime–boost combinations, in C57BL/6 and BALB/c mice. Both vaccines induced strong antigen-specific immune responses, with the heterologous prime–boost regimen eliciting the strongest effects and conferring the most robust and consistent protection across both mouse strains. Immunization triggered a predominantly Th1-skewed response characterized by significantly elevated IFN-γ production, accompanied by balanced antigen-specific IgG responses. Moreover, vaccinated mice developed rapid and potent cytotoxic T lymphocyte (CTL) responses. Following challenge with the RH and PRU strains, vaccinated mice exhibited prolonged survival and significantly reduced brain cyst burdens following PRU challenge compared with control groups. Collectively, these findings indicate that GRA35-based nucleic acid vaccines, particularly when administered in a heterologous prime–boost regimen, elicit multifaceted protective immune responses and represent promising vaccine candidates against T. gondii infection. Full article

Toxoplasma gondii, an obligate intracellular protozoan infecting approximately one-third of the global population, poses a significant yet underappreciated threat to reproductive health in both sexes. Although this parasite has long been linked to birth defects caused by infection during pregnancy, new research shows that it also reduces fertility in both sexes through different but related mechanisms. This review synthesizes knowledge on T. gondii-induced reproductive pathology across females and males, examining shared mechanistic themes while respecting tissue-specific differences, and evaluates emerging therapeutic strategies. In females, the parasite establishes persistent uterine reservoirs, triggers decidual immune dysregulation characterized by NK cell cytotoxicity, M1 macrophage polarization, Treg apoptosis, and inflammasome-mediated pyroptosis, while disrupting estrogen and progesterone signaling through both host receptor modulation and intrinsic parasite steroidogenic enzymes (TgCYP450mt, TgMAPR, Tg-HSD). In males, T. gondii breaches the blood–testis barrier, induces germ cell and Leydig cell apoptosis via ER stress and caspase pathways, impairs sperm quality parameters across acute and chronic infection, and disrupts the hypothalamic–pituitary–gonadal axis. Conserved molecular mechanisms—including NLRP3 inflammasome activation, PERK/eIF2α/ATF4/CHOP-mediated ER stress, and oxidative stress—operate in both reproductive tissues. The parasite’s intrinsic steroidogenic capability and bidirectional hormonal manipulation represent a paradigm shift in understanding host–parasite interactions. Conventional antiparasitics face limitations due to poor reproductive sanctuary penetration. Immunomodulatory approaches targeting Trem2, Tim-3, and the NLRP3 inflammasome show promise, along with natural products including Inonotus obliquus polysaccharide and ginseng polysaccharide. Nanomedicine platforms and mRNA vaccine candidates offer new directions for overcoming tissue barrier limitations. Toxoplasma gondii represents a fundamental threat to fertility and pregnancy outcomes rather than merely a risk for congenital infection. Integrated therapeutic strategies addressing direct parasitism, immunopathology, and endocrine disruption are needed. Longitudinal cohort studies, strain-specific mechanistic comparisons, and clinical trials of immunomodulatory adjuncts are urgently required. Full article

Toxoplasma gondii, the causative agent of toxoplasmosis, a disease widely distributed, is an intracellular parasite that invades host cells of different tissues using specialized endocytic activity. Recent studies suggest that tunneling nanotubes (TNTs), thin cell-surface projections, may participate in the parasite–host cell interaction. Here we report results that suggest the involvement of host-cell TNTs in the adhesion of T. gondii tachyzoites to epithelial LLC-MK² cells. Microscopy analysis showed that incubating cells in a medium containing 0.45 M sucrose induces reversible assembly of TNTs without affecting cell viability. The presence of extended TNTs correlated with increased parasite adhesion and reduced parasite entry, thus suggesting a structural or signaling role in mediating adhesion. TNTs assembled following sucrose incubation contain both actin and tubulin components as determined by immunofluorescence microscopy. These results highlight a possible functional relevance of TNTs in T. gondii host cell interaction, especially in parasite adhesion, opening new perspectives for understanding T. gondii-host cell interaction. Full article

Toxoplasma gondii is an intracellular protozoan transmitted via environmentally resistant oocysts present in food and water, as well as through the consumption of meat containing infective bradyzoites. This study evaluated the inactivation of T. gondii oocysts and bradyzoites (ME-49 strain) by Pulsed Electric Field technology (PEF). Treatment efficacy was determined by mouse bioassay combining brain qPCR and indirect immunofluorescence (IFA), with complementary qPCR in Hs27 cells. The infectious dose (ID₅₀) of T. gondii was estimated at 34.6 oocysts. PEF-treated oocysts (15 kV/cm; 50 kJ/kg; 225 µs) showed a significant reduction in infectivity compared with untreated controls; accordingly, the dose required to establish infection increased to 85.3 oocysts after PEF treatment. Brain qPCR and IFA were highly correlated, whereas heart tissue was less sensitive. Bradyzoites recovered from PEF-treated meat (3.3 kV/cm; 27 kJ/kg; 1600 µs) showed a 50% infectivity reduction compared with untreated samples. In vitro assays confirmed an in vivo reduction in infectivity, indicating that cell cultures can serve as an ethical and efficient tool for preliminary viability assessment. This is the first evidence of T. gondii inactivation by PEF, highlighting its potential as a non-thermal strategy. Further studies are needed to optimize treatment parameters. Full article

Background: The NF-κB signaling pathway plays a critical role in innate immune defense against infections. However, many pathogens secrete toxins or effectors into host cells to manipulate cellular functions for their survival and proliferation. Toxoplasma gondii is known to establish chronic infections by employing sophisticated immune evasion strategies. Dense granule (GRA) proteins are essential for the survival and pathogenesis of T. gondii. Methods: In this study, plasmid transfection, cell culture, luciferase reporter assay, quantitative PCR, and western blot were employed to identify T. gondii GRA proteins that regulate the NF-κB pathway. Results: We demonstrate that GRA12, a specific GRA protein, significantly inhibits NF-κB promoter activity and the transcriptional expression of key cytokines, including IL-6, IL-12, TNF-α, and IFN-β. Western blot analysis further revealed that GRA12 suppresses the activation of the IKK complex and p65. Moreover, GRA12 prevents the nuclear translocation of p65. Conclusions: Our findings demonstrate that GRA12 is involved in immune evasion by inhibiting the NF-κB pathway, thereby facilitating T. gondii dissemination and infection. Full article

Toxoplasmosis is a widely distributed zoonosis caused by the protozoan parasite Toxoplasma gondii. Infection during pregnancy is a major public health concern due to its potential impact on both maternal health and fetal development. Early detection of maternal infection is critical to prevent adverse outcomes; however, maternal signs are often subtle, non-specific or absent, complicating timely diagnosis. This scoping review aimed to map and synthesise existing evidence on early maternal signs, pregnancy and foetal outcomes, frequently assessed risk factors, and diagnostic approaches of toxoplasmosis in expectant mothers in Africa. The review was done in accordance with the PRISMA-ScR guidelines. A literature search of PubMed, Scopus, ResearchGate, and Google Scholar was performed to identify studies published between 2000 and 2025. Retrieved records were managed using Zotero (version 8.0.4) for deduplication and screening. Only English-language studies conducted in Africa and reporting relevant maternal or clinical data were included. A total of 28 cross-sectional studies were included. Lymphadenopathy (25.0%) was the most frequently reported maternal early sign, followed by flu-like illness, asymptomatic infection, low-grade or mild fever, and fatigue or malaise (each 10.7%). Congenital anomalies (50.0%) and miscarriage or spontaneous abortion (42.9%) were the most commonly reported foetal and pregnancy outcomes. Frequently reported risk factors were exposure to cat faeces (57.1%) and ingestion of undercooked or raw meat (42.9%). Diagnostic approaches were commonly enzyme-based immunoassays (78.6%), with limited use of RDTs and molecular methods. These findings suggest the need for improved early detection and prevention strategies in high-risk, low-resource African settings. Enhancing routine screening, health education, and access to appropriate diagnostics are considered. Future studies should consider adopting standardised reporting and integrating sensitive, affordable, rapid diagnostic approaches to enhance early detection and reduce the burden of congenital toxoplasmosis. Full article

Gliomas are aggressive brain tumors with poor prognosis. The contribution of Toxoplasma gondii (T. gondii)-related transcriptional programs to glioma remains unclear. We identified T. gondii infection-related genes from neuroepithelial cell transcriptomes, mapped them to TCGA and CGGA glioma datasets, and validated their expression via RT-qPCR. A prognostic signature (TGRisk) was constructed via Cox and LASSO regression and validated across independent cohorts. Functional, immune, and drug sensitivity analyses were conducted. Forty infection-related genes were identified, enriched in stress responses, microRNA regulation, ribosome biogenesis, and metabolism. The 13-gene TGRisk model significantly separated survival between high- and low-risk groups. A nomogram combining TGRisk with clinical features improved prediction accuracy. High-risk tumors showed immune activation and higher infiltration of CD8⁺ T cells, Tregs, macrophages, and neutrophils, while low-risk tumors showed enhanced neuronal signaling and NK cell activity. Drug sensitivity prediction suggested low-risk patients were more responsive to temozolomide and bortezomib, whereas high-risk patients were more sensitive to dasatinib and ruxolitinib. We developed a novel T. gongdii infection-related gene signature that stratifies glioma patients by prognosis, immune features, and therapeutic vulnerabilities. These findings suggest host–T. gondii interactions and a potential biomarker for patient stratification and personalized therapy. Full article