3-Methyladenine blocks Toxoplasma gondii division prior to centrosome replication.


:The apicomplexan Toxoplasma gondii replicates by endodyogeny, in which replicated organelles assemble into nascent daughter buds within the maternal parasite. The mechanisms governing this complex sequence are not understood. We now report that the kinase inhibitor 3-methlyadenine (3-MA) efficiently blocks T. gondii replication. The inhibition could not be attributed to the effects of 3-MA on mammalian phosphatidylinositol 3-kinase and host cell autophagy. Furthermore, we show that accumulation of host lysosomes around the parasitophorous vacuoles was unaffected. Most 3-MA-treated parasites failed to form daughter buds or replicate DNA, indicating arrest in G1 or early S-phase. Some 3-MA-treated parasites displayed abortive cell division, in which nuclear segregation to malformed daughter buds was incomplete or asymmetrical. Electron microscopy revealed the presence of residual body-like structures in many vacuoles, even in the absence of daughter buds. Most treated parasites had otherwise normal morphology and were able to resume replication upon drug removal. 3-MA-treated and control parasites were similar with respect to the extent of Golgi body division and apicoplast elongation; however, treated parasites rarely possessed replicated centrosomes or apicoplasts. These data are suggestive of a generalized blockade of T. gondii cell cycle progression at stages preceding centrosome replication, rather than arrest at a specific checkpoint. We hypothesize that 3-MA treatment triggers a cell cycle pause program that may serve to protect parasites during periods, such as subsequent to egress, when cell cycle progression might be deleterious. Elucidation of the mechanism of 3-MA inhibition may provide insight into the control of parasite growth.


Mol Biochem Parasitol


Wang Y,Karnataki A,Parsons M,Weiss LM,Orlofsky A




Has Abstract


2010-10-01 00:00:00














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    authors: Borst P,Fase-Fowler F,Gibson WC

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    authors: Takle GB,O'Connor J,Young AJ,Cross GA

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    pub_type: 杂志文章


    authors: Carnall N,Webb H,Carrington M

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    authors: Sidjanski SP,Vanderberg JP,Sinnis P

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    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章,评审


    authors: Simpson L

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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Goodyer ID,Pouvelle B,Schneider TG,Trelka DP,Taraschi TF

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    pub_type: 杂志文章


    authors: Ng JS,Ryan U,Trengove RD,Maker GL

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    pub_type: 杂志文章


    authors: Wisnewski N,McNeil M,Grieve RB,Wassom DL

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    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Park JH,Brekken DL,Randall AC,Parsons M

    更新日期:2002-01-01 00:00:00

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    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Muhammad N,Suleman,Khan MS,Li L,Zhao Q,Ullah H,Zhu XQ,Ma J

    更新日期:2020-05-01 00:00:00

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    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Jiang L,Duriseti S,Sun P,Miller LH

    更新日期:2009-11-01 00:00:00

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    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Campos MC,Leon LL,Taylor MC,Kelly JM

    更新日期:2014-01-01 00:00:00

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    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Ghoda LY,Savarese TM,Northup CH,Parks RE Jr,Garofalo J,Katz L,Ellenbogen BB,Bacchi CJ

    更新日期:1988-01-15 00:00:00