Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma Gondii DOI Creative Commons
Deqi Yin, Ning Jiang, Chang Cheng

et al.

Genomics Proteomics & Bioinformatics, Journal Year: 2022, Volume and Issue: 21(6), P. 1163 - 1181

Published: Oct. 7, 2022

Abstract The biology of Toxoplasma gondii, the causative pathogen one most widespread parasitic diseases (toxoplasmosis), remains poorly understood. Lactate, which is derived from glucose metabolism, not only an energy source in a variety organisms, including T. but also regulatory molecule that participates gene activation and protein function. Lysine lactylation (Kla) type post-translational modifications (PTMs) has been recently associated with chromatin remodeling; however, Kla histone non-histone proteins yet studied gondii. To examine prevalence function gondii parasites, we mapped lactylome proliferating tachyzoite cells identified 1964 sites on 955 RH strain. Lactylated were distributed multiple subcellular compartments closely related to wide biological processes, mRNA splicing, glycolysis, aminoacyl-tRNA biosynthesis, RNA transport, many signaling pathways. We performed immunoprecipitation sequencing (ChIP-seq) analysis using lactylation-specific antibody found histones H4K12la H3K14la enriched promoter exon regions microtubule-based movement cell invasion. further confirmed delactylase activity deacetylases TgHDAC2–4, treatment anti-histone acetyltransferase (TgMYST-A) antibodies profoundly reduced This study offers first dataset global proteome provides basis for dissecting functional

Language: Английский

The molecular architecture of the nuclear basket DOI Creative Commons
Digvijay Singh, Neelesh Soni, Joshua Hutchings

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5267 - 5281.e13

Published: Aug. 9, 2024

The nuclear pore complex (NPC) is the sole mediator of nucleocytoplasmic transport. Despite great advances in understanding its conserved core architecture, peripheral regions can exhibit considerable variation within and between species. One such structure cage-like basket. crucial roles mRNA surveillance chromatin organization, an architectural has remained elusive. Using in-cell cryo-electron tomography subtomogram analysis, we explored NPC's structural variations basket across fungi (yeast; S. cerevisiae), mammals (mouse; M. musculus), protozoa (T. gondii). integrative modeling, computed a model yeast that revealed how hub nucleoporins (Nups) ring binds to basket-forming Mlp/Tpr proteins: coiled-coil domains form struts basket, while their unstructured termini constitute distal densities, which potentially serve as docking site for preprocessing before

Language: Английский

Citations

26
Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases DOI Creative Commons
Darine Daher,

Ahmad Shaghlil,

Eyad Sobh

et al.

Pathogens, Journal Year: 2021, Volume and Issue: 10(11), P. 1351 - 1351

Published: Oct. 20, 2021

Toxoplasma gondii (T. gondii) is a prevalent protozoan parasite of medical and veterinary significance. It the etiologic agent toxoplasmosis, neglected disease in which incidence symptoms differ between patients regions. In immunocompetent patients, toxoplasmosis manifests as acute chronic forms. Acute presents mild or asymptomatic that evolves, under host immune response, into persistent healthy individuals. Chronic establishes latent tissue cysts brain skeletal muscles. immunocompromised may reactivate, leading to potentially life-threatening condition. Recently, association various diseases has been shown. These span primary neuropathies, behavioral psychiatric disorders, different types cancer. Currently, direct pre-clinical clinical molecular connotation most its associated remains poorly understood. this review, we provide comprehensive overview on Toxoplasma-induced with focus available knowledge players dictating these associations. We will also abridge existing therapeutic options highlight current gaps explore implications advance treatment modalities.

Language: Английский

Citations

75
Schizophrenia: The new etiological synthesis DOI Creative Commons
Markus J. Rantala, Severi Luoto, Javier I. Borráz-León

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 142, P. 104894 - 104894

Published: Sept. 28, 2022

Schizophrenia has been an evolutionary paradox: it high heritability, but is associated with decreased reproductive success. The causal genetic variants underlying schizophrenia are thought to be under weak negative selection. To unravel this paradox, many explanations have suggested for schizophrenia. We critically discuss the constellation of hypotheses schizophrenia, highlighting lack empirical support most existing hypotheses—with exception relatively well supported mismatch hypothesis. It posits that evolutionarily novel features contemporary environments, such as chronic stress, low-grade systemic inflammation, and gut dysbiosis, increase susceptibility Environmental factors microbial infections (e.g., Toxoplasma gondii) can better predict onset than polygenic risk scores. However, researchers not able explain why only a small minority infected people develop new etiological synthesis indicates interaction between host genotype, microbe infection, stress causes neuroinflammation dysbiosis mediating pathway. Instead just alleviating symptoms drugs, parasite x genotype model emphasizes treatment should focus on detecting treating possible infection(s), neuroinflammation, stress.

Language: Английский

Citations

47
A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells DOI Creative Commons
Eloise J. Lockyer, Francesca Torelli, Simon Butterworth

et al.

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(7), P. e3002202 - e3002202

Published: July 17, 2023

Toxoplasma gondii secretes protein effectors to subvert the human immune system sufficiently establish a chronic infection. Relative murine infections, little is known about which parasite disarm responses. Here, we used targeted CRISPR screening identify secreted required for survival in IFNγ-activated cells. Independent screens were carried out using 2 strains that differ virulence mice, leading identification of We GRA57 and other proteins, GRA70 GRA71, together form complex enhances ability parasites persist foreskin fibroblasts (HFFs). Components machinery export proteins into host cell also found be important resistance IFNγ cells, but these components function independently identified complex. Host-mediated ubiquitination vacuole has previously been associated with increased clearance from find vacuoles GRA57, GRA70, GRA71 knockout are surprisingly less ubiquitinated by cell. hypothesise this likely secondary consequence deletion complex, unlinked mediated effectors.

Language: Английский

Citations

34
Global seroprevalence of Toxoplasma gondii infection among patients with mental and neurological disorders: A systematic review and meta‐analysis DOI Creative Commons
Habtye Bisetegn, Habtu Debash, Hussen Ebrahim

et al.

Health Science Reports, Journal Year: 2023, Volume and Issue: 6(6)

Published: June 1, 2023

Toxoplasmosis is the most widespread zoonotic disease that affects one-third of world's population, and imposes a major public health problem worldwide. This study aimed to assess prevalence toxoplasmosis among patients with neuropsychiatric patients.

Language: Английский

Citations

27
Function and regulation of cGAS-STING signaling in infectious diseases DOI Creative Commons
Yang Du, Zhiqiang Hu,

Yien Luo

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 6, 2023

The efficacious detection of pathogens and prompt induction innate immune signaling serve as a crucial component defense against infectious pathogens. Over the past decade, DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) its downstream adaptor stimulator interferon genes (STING) have emerged key mediators type I (IFN) nuclear factor-κB (NF-κB) responses in health infection diseases. Moreover, both cGAS-STING pathway developed delicate strategies to resist each other for their survival. mechanistic functional comprehension interplay between is opening way development application pharmacological agonists antagonists treatment Here, we briefly review current knowledge DNA sensing through pathway, emphatically highlight potent undertaking host pathogenic organisms.

Language: Английский

Citations

26
Biogenesis of extracellular vesicles in protozoan parasites: The ESCRT complex in the trafficking fast lane? DOI Creative Commons
Abel Cruz Camacho, Daniel Alfandari, Ewa Kozela

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(2), P. e1011140 - e1011140

Published: Feb. 23, 2023

Extracellular vesicles (EVs) provide a central mechanism of cell–cell communication. While EVs are found in most organisms, their pathogenesis-promoting roles parasites particular interest given the potential for medical insight and consequential therapeutic intervention. Yet, key feature human parasitic protozoa remains elusive: mechanisms biogenesis. Here, we survey current knowledge on biogenesis pathways secreted by four main clades protozoa: apicomplexans, trypanosomatids, flagellates, amoebae. In particular, shine light findings pertaining to Endosomal Sorting Complex Required Transport (ESCRT) machinery, as mammals it plays important EV This review highlights diversity protozoa, well related involvement ESCRT system these unique organisms.

Language: Английский

Citations

24
Immune responses to Toxoplasma gondii DOI Creative Commons
Imtiaz A. Khan, Magali Moretto

Current Opinion in Immunology, Journal Year: 2022, Volume and Issue: 77, P. 102226 - 102226

Published: July 1, 2022

Language: Английский

Citations

38
Toxoplasmosis vaccines: what we have and where to go? DOI Creative Commons
Yizhuo Zhang, Dan Li, Shaohong Lu

et al.

npj Vaccines, Journal Year: 2022, Volume and Issue: 7(1)

Published: Oct. 31, 2022

Abstract Despite recent major advances in developing effective vaccines against toxoplasmosis, finding new protective vaccination strategies remains a challenging and elusive goal as it is critical to prevent the disease. Over past few years, various experimental approaches have shown that an vaccine T. gondii achievable. However, more unknown due its complicated life cycle, difficulties clinical translation, lack of standardized platform. This minireview summarizes development main obstacles safe, durable vaccine. The successes failures testing candidates for are also discussed, which may facilitate future vaccines.

Language: Английский

Citations

37
Toxoplasma gondii in Foods: Prevalence, Control, and Safety DOI Creative Commons
Pablo Jesús Marín‐García, Núria Planas, Lola Llobat

et al.

Foods, Journal Year: 2022, Volume and Issue: 11(16), P. 2542 - 2542

Published: Aug. 22, 2022

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, with approximately one third of the population around world seropositive. The consumption contaminated food main source infection. These include meat products T. tissue cysts, and dairy tachyzoites. Recently, contamination has been detected in fresh oocysts marine products. Despite great health problems are caused by gondii, currently there no standardized methods for its detection industry. In this review, we analyze current methods, prevalence different products, control measures. bioassays, cell culture, molecular microscopic techniques, serological but some these do not have applicability As a result, emerging techniques being developed aimed at multiple parasites simultaneously would make their application more efficient Since high many (meat milk, vegetables), it necessary to standardize as well implement

Language: Английский

Citations

34