A change in the premitotic period of the cell cycle is associated with bradyzoite differentiation in Toxoplasma gondii

Radke, Jay R.; Guerini, Michael N.; Jerome, Maria; White, Michael

doi:10.1016/s0166-6851(03)00198-1

Cited by 106 publications

(154 citation statements)

References 40 publications

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“…The populations of bradyzoites used in this study were likely in different stages of the cell cycle; in vivo bradyzoites are believed to be dividing at a much lower rate than tachyzoites, and so a greater fraction of the former are likely in the G 1 or G 0 (arrested) stage of the cell cycle, whereas parasites transitioning from the tachyzoite to the bradyzoite stage in vitro have many cells in late S/G 2 , a difference that may be key to the differentiation process (21,39,48). Work by Behnke et al has demonstrated distinct subtranscriptomes in tachyzoites as they progress through the cell cycle (5).…”

Section: Discussionmentioning

confidence: 99%

Identification of Tissue Cyst Wall Components by Transcriptome Analysis of In Vivo and In Vitro Toxoplasma gondii Bradyzoites

et al. 2011

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The Toxoplasma gondii bradyzoite is essential to establish persistent infection, yet little is known about what factors this developmental form secretes to establish the cyst or interact with its host cell. To identify candidate bradyzoite-secreted effectors, the transcriptomes of in vitro tachyzoites 2 days postinfection, in vitro bradyzoites 4 days postinfection, and in vivo bradyzoites 21 days postinfection were interrogated by microarray, and the program SignalP was used to identify signal peptides indicating secretion. One hundred two putative bradyzoite-secreted effectors were identified by this approach. Two candidates, bradyzoite pseudokinase 1 and microneme adhesive repeat domain-containing protein 4, were chosen for further investigation and confirmed to be induced and secreted by bradyzoites in vitro and in vivo. Thus, we report the first analysis of the transcriptomes of in vitro and in vivo bradyzoites and identify two new protein components of the Toxoplasma tissue cyst wall.

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Section: Discussionmentioning

confidence: 99%

Identification of Tissue Cyst Wall Components by Transcriptome Analysis of In Vivo and In Vitro Toxoplasma gondii Bradyzoites

et al. 2011

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“…Toxoplasma succeeds in this daunting task by using a variety of strategies applied by microbial agents, which allow them to persist until transmission to a new host (by carnivorism for Toxoplasma) can be accomplished. Such strategies include: modification of the intracellular environment within host cells to favor parasite survival (7); manipulation of the host immune response by producing immunomodulatory molecules (8,9); establishment of chronic infection predominantly in the brain, where immune surveillance is controlled differently than in other peripheral tissues (10); and, the fact that BZs are metabolically quiescent and relatively nonproliferative during chronic infection (11).…”

Section: Stage-specific Expression Of Surface Antigens Bymentioning

confidence: 99%

Stage-Specific Expression of Surface Antigens by Toxoplasma gondii as a Mechanism to Facilitate Parasite Persistence

Kim

Boothroyd

2005

The Journal of Immunology

105

106

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Toxoplasma persists in the face of a functional immune system. This success critically depends on the ability of parasites to activate a strong adaptive immune response during acute infection with tachyzoites that eliminates most of the parasites and to undergo stage conversion to bradyzoites that encyst and persist predominantly in the brain. A dramatic change in antigenic composition occurs during stage conversion, such that tachyzoites and bradyzoites express closely related but antigenically distinct sets of surface Ags belonging to the surface Ag 1 (SAG1)-related sequence (SRS) family. To test the contribution of this antigenic switch to parasite persistence, we engineered parasites to constitutively express the normally bradyzoite-specific SRS9 (SRS9c) mutants and tachyzoite-specific SAG1 (SAG1c) mutants. SRS9c but not wild-type parasites elicited a SRS9-specific immune response marked by IFN-γ production, suggesting that stage-specificity of SRS Ags determines their immunogenicity in infection. The induction of a SRS9-specific immune response correlated with a continual decrease in the number of SRS9c cysts persisting in the brain. In contrast, SAG1c mutants produced reduced brain cyst loads early in chronic infection, but these substantially increased over time accompanying a hyperproduction of IFN-γ, TNF-α, and IL-10, and severe encephalitis. We conclude that stage-specific expression of SRS Ags is among the key mechanisms by which optimal parasite persistency is established and maintained.

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“…Despite the importance of growth mechanisms in Toxoplasma -caused disease, we know very little about the regulation of the parasite cell cycle or how growth mechanisms are linked to parasite development. It has long been established that differentiation of tachyzoites-to-bradyzoites is accompanied by a change to a slower parasite growth rate (Soete et al ., 1993;Bohne et al ., 1994) which is programmed (Jerome et al ., 1998;Radke et al ., 2003) and obligatory to development as fast growing mutant strains do not spontaneously differentiate but will do so if their growth is slowed by drug or stress treatment (Soete et al ., 1993;Bohne et al ., 1994). These and other findings (Jerome et al ., 1998) indicate that molecular switches link the growth rate and number of parasite divisions to the developmental fate of this organism, and therefore, studies of the parasite cell cycle are crucial to understand chronic as well as acute disease.…”

Section: Introductionmentioning

confidence: 99%

Genetic rescue of a Toxoplasma gondii conditional cell cycle mutant

White

Jerome

Vaishnava

et al. 2005

Molecular Microbiology

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SummaryGrowth rate is a major pathogenesis factor in the parasite Toxoplasma gondii ; however, how cell division is controlled in this protozoan is poorly understood. Herein, we show that centrosomal duplication is an indicator of S phase entry while centrosome migration marks mitotic entry. Using the pattern of centrosomal replication, we confirmed that mutant ts 11C9 undergoes a bimodal cell cycle arrest that is characterized by two subpopulations containing either single or duplicated centrosomes which correlate with the bipartite genome distribution observed at the non-permissive temperature. Genetic rescue of ts 11C9 was performed using a parental RH strain cDNA library, and the cDNA responsible for conferring temperature resistance (growth at 40 ∞ ∞ ∞ ∞ C) was recovered by recombination cloning. A single T. gondii gene encoding the protein homologue of XPMC2 was responsible for genetic rescue of the temperature-sensitive defect in ts 11C9 parasites. This protein is a known suppressor of mitotic defects, and in tachyzoites, TgXPMC2-YFP localized to the parasite nucleus and nucleolus which is consistent with the expected subcellular localization of critical mitotic factors. Altogether, these results demonstrate that ts 11C9 is a conditional mitotic mutant containing a single defect which influences two distinct control points in the T. gondii tachyzoite cell cycle.

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A change in the premitotic period of the cell cycle is associated with bradyzoite differentiation in Toxoplasma gondii

Cited by 106 publications

References 40 publications

Identification of Tissue Cyst Wall Components by Transcriptome Analysis of In Vivo and In Vitro Toxoplasma gondii Bradyzoites

Identification of Tissue Cyst Wall Components by Transcriptome Analysis of In Vivo and In Vitro Toxoplasma gondii Bradyzoites

Stage-Specific Expression of Surface Antigens by Toxoplasma gondii as a Mechanism to Facilitate Parasite Persistence

Genetic rescue of a Toxoplasma gondii conditional cell cycle mutant

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