Dataset Information

AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment

ABSTRACT: Toxoplasma gondii is a ubiquitous protozoan with a complex life cycle involving transitions between different hosts and developmental stages, each adapted to a unique niche within its host. However, the regulatory mechanisms controlling these life cycle transitions remain poorly understood. In this study, we characterized the AP2 factor AP2X-1, which is expressed during the tachyzoite and bradyzoite stages, but not in the mature merozoite stage. Knockout of ap2X-1 significantly impaired tachyzoite invasion and replication, while increasing the frequency of bradyzoite differentiation. As a component of the HDAC3/MORC complex, knockout of ap2X-1 led to the upregulation of bradyzoite and sexual stage-specific genes. Single-cell sequencing revealed that ap2X-1 knockout strains behaved as a mixed population of tachyzoites, bradyzoites, merozoites, and sporozoites. CUT&Tag analysis revealed substantial overlap between AP2X-1 and HDAC3/MORC complex binding at the promoters of bradyzoite and sexual stage-specific genes. Additionally, ATAC-seq analysis demonstrated that AP2X-1 modulates chromatin compaction and accessibility, suggesting that AP2X-1 recruits the HDAC3/MORC complex to repress bradyzoite differentiation and sexual commitment. The loss of ap2X-1 resulted in significant attenuation of T. gondii virulence and reduced the formation of brain cysts in vivo. These findings identify AP2X-1 as a critical negative regulator of T. gondii sexual development.

ORGANISM(S): Toxoplasma gondii

PROVIDER: GSE249123 | GEO | 2025/06/25

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Toxoplasma gondii, a protozoan parasite, causes toxoplasmosis, a widespread zoonotic and food-borne infection that poses significant risks, particularly in opportunistic and congenital cases. This obligate intracellular parasite is highly prevalent worldwide, largely due to its versatile life cycle, involving multiple hosts and transmission routes, and its ability to establish chronic infections. The presence of this neurotropic parasite in the brain poses a reactivation risk in immunocompromised individuals and might be associated with a higher likelihood of developing mental disorders. However, the role of the dormant bradyzoite stage in the pathophysiology of the disease is underexplored, mainly due to the lack of non-invasive detection methods and serologic tests targeting bradyzoite- or cyst-specific antigens. In this study, we performed an unbiased screening of the bradyzoite proteome and identified the Bradyzoite Serological Marker (BSM) as an additional serological biomarker, alongside the cyst-associated BCLA, to detect chronic stages in vivo. BSM and BCLA show high sensitivity and specificity in identifying cyst-bearing mice. However, in humans, these markers exhibit only moderate concordance, with a 30% positivity rate among individuals with prior immunity, suggesting variability in immune responses and complexities in diagnosing chronic toxoplasmosis. Importantly, bradyzoite serology helps differentiate recent from past infections by the teratogenic parasite Toxoplasma gondii, with BCLA improving the accuracy of pergestational infection diagnosis. Exploring the regulatory mechanisms controlling the expression of these markers revealed that the chromatin modifiers MORC and HDAC3 exert epistatic control over BFD1, a key regulator of bradyzoite development. While BFD1 governs a specific subset of bradyzoite markers, including BCLA, a sub-transcriptome comprising BSM relies on MORC/HDAC3 independently of BFD1. This complex gene regulation highlights the challenge in understanding Toxoplasma persistence, while offering new opportunities for improved serological diagnosis of congenital and chronic toxoplasmosis, particularly in individuals with mental health conditions or a risk of toxoplasmic reactivation.

Dataset Information

AP2X-1 is a negative regulator of Toxoplasma gondii sexual commitment

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets