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In vitro production of cat-restricted Toxoplasma pre-sexual stages
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Journal Article
In vitro production of cat-restricted Toxoplasma pre-sexual stages
2024
Overview
Sexual reproduction of
Toxoplasma gondii
, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described
1
,
2
. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref.
1
), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on
Toxoplasma
sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission.
A study describes the molecular basis of sexual development of
Toxoplasma gondii
entirely in vitro, demonstrating the role and interaction of AP2XII-1 and AP2XI-2 in the developmental program of this protozoan parasite.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/15
/ 38/39
/ 38/91
/ 82
/ 82/51
/ 82/58
/ 82/83
/ 96
/ 96/1
/ Animals
/ Gametes
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ In Vitro Techniques - methods
/ Life Cycle Stages - genetics
/ Nuclear Proteins - metabolism
/ Principal components analysis
/ Promoter Regions, Genetic - genetics
/ Proteins
/ Protozoan Proteins - genetics
/ Protozoan Proteins - metabolism
/ Science
/ Toxoplasma - growth & development
/ Toxoplasmosis - parasitology
