PP1 phosphatase controls both daughter cell formation and amylopectin levels in Toxoplasma gondii DOI Creative Commons

Asma S. Khelifa,

M. Bhaskaran,

Tom Boissavy

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(9), P. e3002791 - e3002791

Published: Sept. 10, 2024

Virulence of apicomplexan parasites is based on their ability to divide rapidly produce significant biomass. The regulation cell cycle therefore key pathogenesis. Phosphorylation a crucial posttranslational modification that regulates many aspects the eukaryotic cycle. phosphatase PP1 known play major role in phosphorylation balance eukaryotes. We explored TgPP1 during tachyzoite form parasite Toxoplasma gondii. Using conditional mutant strain, we show including proper assembly daughter cells' inner membrane complex (IMC), segregation organelles, and nuclear division. Unexpectedly, depletion also results accumulation amylopectin, storage polysaccharide usually found latent bradyzoite parasite. transcriptomics phospho-proteomics, mainly acts through mechanisms by dephosphorylating target proteins IMC proteins. dephosphorylates protein bearing starch-binding domain. Mutagenesis analysis reveals targeted phospho-sites are linked regulate amylopectin steady-state levels. Therefore, has pleiotropic roles regulation, but accumulation.

Language: Английский

A positive feedback loop controls Toxoplasma chronic differentiation DOI

M. Haley Licon,

Christopher J. Giuliano, Alex W Chan

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(5), P. 889 - 904

Published: April 20, 2023

Language: Английский

Citations

42
The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony DOI Creative Commons
Jin‐Lei Wang, Tingting Li, Nian‐Zhang Zhang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 26, 2024

Abstract Sexual development in Toxoplasma gondii is a multistep process that culminates the production of oocysts, constituting approximately 50% human infections. However, molecular mechanisms governing sexual commitment this parasite remain poorly understood. Here, we demonstrate transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual during asexual development. Depletion type II Pru strain induces merogony mature merozoites an alkaline medium but not neutral medium. In contrast, AP2XII-1-depleted undergoes several rounds produces medium, with more pronounced effects observed under conditions. Additionally, identified two additional AP2XI-2-interacting proteins involved repressing merozoite programming. These findings underscore intricate regulation by network suggest or parasites can serve model for studying vitro.

Language: Английский

Citations

18
The plant-like protein phosphatase PPKL regulates parasite replication and morphology in Toxoplasma gondii DOI Creative Commons

Xi-Ting Wu,

Xuwen Gao,

Qiangqiang Wang

et al.

Parasites & Vectors, Journal Year: 2024, Volume and Issue: 17(1)

Published: March 18, 2024

Abstract Background The protozoan parasite Toxoplasma gondii encodes dozens of phosphatases, among which a plant-like phosphatase absent from mammalian genomes named PPKL, is involved in regulating brassinosteroid signaling Arabidopsis , was identified the genome. Among Apicomplexa parasites, T. an important and representative pathogen humans animals. PPKL previously to modulate apical integrity morphology ookinetes motility transmission another parasite, Plasmodium falciparum . However, exact function asexual stages remains unknown. Methods plant auxin-inducible degron (AID) system applied dissect phenotypes We first analyzed AID parasites at induction time 24 h, by staining different organelles using their corresponding markers. These analyses were further conducted for grown auxin 6 12 h quantitative approach type II strain ME49 parasites. To understand phenotypes, potential protein interactions proximity biotin labeling approach. essential role replication revealed. Results localized region nucleus partially distributed cytoplasm parasite. phenotyping showed its essentiality morphology. Further dissections demonstrate that required maturation daughter mother cells, resulting multiple nuclei single phenotype observed ME49. substantial defect could be rescued genetic complementation, thus supporting formation interaction analysis with diverse proteins, explaining importance Conclusions plays revealing subtle involvement proper during division. Our detailed also demonstrated depletion resulted elongated tubulin fibers roles are potentially attributed mediated kelch domains on protein. Taken together, these findings contribute our understanding key replication, suggesting this as pharmaceutic target. Graphical

Language: Английский

Citations

4
Global Research Landscape and Trends in Toxoplasma gondii from 2003 to 2022: A Bibliometric Analysis DOI
Shijie Fan, Ming Pan, Chenxi Xia

et al.

Veterinary Parasitology, Journal Year: 2025, Volume and Issue: 335, P. 110438 - 110438

Published: Feb. 27, 2025

Language: Английский

Citations

0
Spatiotemporal Diffusion, Colonization, and Antibody Responses in Susceptible C57BL/6J Mice Orally Infected with Toxoplasma gondii Cysts DOI Creative Commons
Zhao Li, Qi-Shuai Liu, Junjie Hu

et al.

Veterinary Sciences, Journal Year: 2025, Volume and Issue: 12(3), P. 212 - 212

Published: March 1, 2025

Toxoplasma gondii is an obligate intracellular protozoan that infects humans and other mammals. The C57BL/6J mouse strain regarded as ideal model organism for studying T. due to its susceptibility infection advantages over laboratory animals. However, systematic studies on the response dynamics of susceptible mice after oral with cysts are lacking. To address this research gap, we investigated spatiotemporal infection, colonization, antibody fluctuations in orally infected Type II ME49 cysts. Mice were challenged examine dynamics. Daily monitoring was conducted 60 days post-infection (dpi) assess animals’ clinical signs survival rates. parasite burden various organs quantified using qPCR targeting B1 gene. serum responses evaluated ELISA. cyst brain assessed via histology immunofluorescence. induced symptoms mice, including fever weight loss. rapidly invaded mice’s small intestine, spleen, lungs, liver, heart bloodstream within 1–5 dpi. had breached blood–brain barrier colonized by 7 levels Toxoplasma-specific IgG antibodies increased stabilized two months (until experiment ended). Systemic dissemination occurred rapidly, infiltrating most tissues organs, leading pronounced enteritis multi-organ damage inflammation. tachyzoites differentiated into bradyzoites when progressed from acute chronic phase forming tissue muscles brain. As a result, predilection site brain, which where persisted host’s lifetime continuously meningitis. These findings provide valuable insights diffusion, sites, temporal dynamics, pathogen detection methodologies, histopathological changes following important elucidating gondii’s pathogenesis host–T. interaction.

Language: Английский

Citations

0
AP2XII‐9 is essential for parasite growth and suppresses bradyzoite differentiation in Toxoplasma gondii DOI

Xiaojing Wu,

Meng Wang,

N.Z. Zhang

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(6)

Published: March 19, 2025

Cyst formation, resulting from the differentiation of rapidly replicating tachyzoites into slowly growing bradyzoites, is primary cause chronic toxoplasmosis. Although mechanisms governing bradyzoite have been partially elucidated, they remain incompletely understood. In this study, we show that transcription factor AP2XII-9 localized in nucleus and exhibits periodic expression during tachyzoite stage, with peak observed synthesis mitosis phases. Conditional knockdown both type I RH strain II cyst-forming Pru revealed plays a critical role lytic cycle by regulating formation inner membrane complex, proper apicoplast inheritance, normal cell division, underscoring its essential T. gondii growth. Furthermore, depletion induced even absence alkaline stress. Transcriptomic analysis deletion resulted downregulation growth-related genes upregulation series bradyzoite-specific genes. Taken together, these findings indicate for maintaining rapid replication while actively repressing differentiation, reflecting complexity underlying differentiation.

Language: Английский

Citations

0
Phosphatase UBLCP1 is required for the growth, virulence and mitochondrial integrity of Toxoplasma gondii DOI Creative Commons

Kaiyin Sheng,

Kaiyue Song,

Yimin Yang

et al.

Parasites & Vectors, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 28, 2025

Abstract Background The mitochondrion is proposed as an ideal target organelle for the control of apicomplexan parasites, whose integrity depends on well-controlled protein import, folding, and turnover. ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) was found to be associated with mitochondrial in Toxoplasma gondii . However, little known about roles mechanisms UBLCP1 this parasite. Methods subcellular localization tachyzoites T. determined by indirect immunofluorescence assay. growth, cell cycle, division were assessed knocking out molecule tachyzoites. Comparative phosphoproteomics between UBLCP1-deficient wild-type performed understand virulence tested mice. Results expressed nucleus cytoplasm Tachyzoites lacking exhibit collapsed mitochondrion, decreased membrane potential, compromised growth proliferation vitro. Proteins involved turnover intracellular trafficking have been differentially phosphorylated compared control. Deletion also shows that essential propagation Mice immunized survived challenges virulent PRU or VEG strain. Conclusions required lytic cycle (e.g., host invasion parasite replication) vitro pathogenicity vivo. a candidate vaccine drug toxoplasmosis animals. Graphical

Language: Английский

Citations

0
Functions of Posttranslational Modifications in Toxoplasma gondii and Their Potential as Drug Targets DOI Creative Commons
Chenghuan Li, Xing‐Quan Zhu, Qijun Chen

et al.

Transboundary and Emerging Diseases, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Toxoplasma gondii is an obligate intracellular apicomplexan parasite. Currently, the effective drugs for treatment of toxoplasmosis are mainly pyrimethamine and sulfonamide, but these have high toxicity side effects, so search new drug targets urgent. Posttranslational modifications (PTMs) certain chemical groups that covalently coupled to specific amino acids within a protein. Studies shown T. expresses variety proteins require PTMs regulate parasite’s response extracellular stimuli life cycle transitions at different developmental stages. In this review, we summarize analyze 14 been found in date their roles growth development. addition, discuss potential crosstalk between stages results studies on inhibitors target PTM regulatory factors. The aim further functions development pathogenesis lay foundation anti‐ targets.

Language: Английский

Citations

0
Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness DOI Creative Commons
Zhiwei Zhang, Meng Wang,

Li‐Xiu Sun

et al.

Parasites & Vectors, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 4, 2024

Abstract Background To successfully replicate within the host cell, Toxoplasma gondii employs several mechanisms to overcome cell defenses and mitigate harmful effects of free radicals resulting from its own metabolic processes using effectors such as thioredoxin proteins. In this study, we characterize location functions a newly identified in T. , which was named Trx4. Methods We characterized functional role Trx4 Type I RH II Pru strains by gene knockout studied subcellular localization endogenous protein HA tagging CRISPR-Cas9 editing. The enzyme-catalyzed proximity labeling technique, TurboID system, employed identify proteins Results dense granule predominantly expressed parasitophorous vacuole (PV) partially co-localized with GRA1 GRA5. Functional analysis showed that deletion trx4 markedly influenced parasite lytic cycle, impaired invasion capacity both strains. Mutation Trx domains strain revealed two were important for invasion. By utilizing system biotinylate Trx4, substantial number proteins, some are novel, others previously characterized, distributed granules. addition, uncovered three novel Intriguingly, did not affect these Finally, virulence assay demonstrated resulted significant attenuation reduction brain cyst loads mice. Conclusions plays an strain. Combining technique many PV-localized associated These findings suggest versatile mediating occur distinctive intracellular membrane-bound vacuolar compartment. Graphical

Language: Английский

Citations

3
A Gwas Approach to Identify Novel Major-Effect Qtls for End-Use Quality Traits in Soft Red Winter Wheat DOI Open Access
Madhav Subedi, John White Bagwell, Benjamín López

et al.

Published: Aug. 15, 2024

Wheat is used for making many food products due to its diverse quality profile found among different wheat classes. Since laboratory analysis of these end-use traits costly and time-consuming, genetic dissection the preferential. This study a genome-wide association (GWAS) 10 traits, including kernel protein, flour yield, softness equivalence, solvent’s retention capacity, cookie diameter, top-grain, in soft red winter (SRWW) adapted US southeast. The GWAS included 266 SRWW genotypes that were evaluated two locations over years (2020-2022). A total 27,466 single nucleotide markers 80 significant marker-trait associations identified. There 13 major effect quantitative trait loci (QTLs) explaining > 10% phenotypic variance out which 12 considered as novel. Five QTLs be stably expressed across multiple datasets, four showed with traits. Candidate genes identified eight major-effect associated starch biosynthesis nutritional homeostasis plants. These findings increase comprehension could potentially improving SRWW.

Language: Английский

Citations

2