The apicoplast is important for the viability and persistence of Toxoplasma gondii bradyzoites - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2023

The apicoplast is important for the viability and persistence of Toxoplasma gondii bradyzoites

Résumé

Toxoplasma gondii is responsible for toxoplasmosis, a disease that can be serious when contracted during pregnancy, but can also be a threat for immunocompromised individuals. Acute infection is associated with the tachyzoite form that spreads rapidly within the host. However, under stress conditions, some parasites can differentiate into cyst-forming bradyzoites, residing mainly in the central nervous system, retina and muscle. Because this latent form of the parasite is resistant to all currently available treatments, and is central to persistence and transmission of the parasite, specific therapeutic strategies targeting this developmental stage need to be found. T. gondii contains a plastid of endosymbiotic origin called the apicoplast, which is an appealing drug target because it is essential for tachyzoite viability and contains several key metabolic pathways that are largely absent from the mammalian host. Its function in bradyzoites, however, is unknown. Our objective was thus to study the contribution of the apicoplast to the viability and persistence of bradyzoites during chronic toxoplasmosis. We have used complementary strategies based on stage-specific promoters to generate conditional bradyzoite mutants of essential apicoplast genes. Our results show that specifically targeting the apicoplast in both in vitro or in vivo-differentiated bradyzoites leads to a loss of long-term bradyzoite viability, highlighting the importance of this organelle for this developmental stage. This validates the apicoplast as a potential area to look for therapeutic targets in bradyzoites, with the aim to interfere with this currently incurable parasite stage.

Dates et versions

inserm-04467177 , version 1 (20-02-2024)

Identifiants

Citer

Syrian Sanchez, Emilie Bassot, Aude Cerutti, Hoa Mai Nguyen, Amel Aïda, et al.. The apicoplast is important for the viability and persistence of Toxoplasma gondii bradyzoites. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 (34), pp.e2309043120. ⟨10.1073/pnas.2309043120⟩. ⟨inserm-04467177⟩
4 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More