Toxoplasma metabolic flexibility in different growth conditions

Walsh, Daniel; Katris, Nicholas J.; Sheiner, Lilach; Botté, Cyrille Y.

doi:10.1016/j.pt.2022.06.001

Cited by 19 publications

(18 citation statements)

References 85 publications

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“…One of the environmental conditions that can have a great impact on the growth and establishment of T. gondii in the host is associated with the availability of nutrients in the different tissues invaded [ 40 ]. Recently, Kloehn et al [ 35 ] analyzed the role of subcellular sub-pools of acetyl-CoA.…”

Section: Resultsmentioning

confidence: 99%

Architecture, Chromatin and Gene Organization of Toxoplasma gondii Subtelomeres

et al. 2022

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Subtelomeres (ST) are chromosome regions that separate telomeres from euchromatin and play relevant roles in various biological processes of the cell. While their functions are conserved, ST structure and genetic compositions are unique to each species. This study aims to identify and characterize the subtelomeric regions of the 13 Toxoplasma gondii chromosomes of the Me49 strain. Here, STs were defined at chromosome ends based on poor gene density. The length of STs ranges from 8.1 to 232.4 kbp, with a gene density of 0.049 genes/kbp, lower than the Me49 genome (0.15 kbp). Chromatin organization showed that H3K9me3, H2A.X, and H3.3 are highly enriched near telomeres and the 5′ end of silenced genes, decaying in intensity towards euchromatin. H3K4me3 and H2A.Z/H2B.Z are shown to be enriched in the 5′ end of the ST genes. Satellite DNA was detected in almost all STs, mainly the sat350 family and a novel satellite named sat240. Beyond the STs, only short dispersed fragments of sat240 and sat350 were found. Within STs, there were 12 functional annotated genes, 59 with unknown functions (Hypothetical proteins), 15 from multigene FamB, and 13 from multigene family FamC. Some genes presented low interstrain synteny associated with the presence of satellite DNA. Orthologues of FamB and FamC were also detected in Neospora caninum and Hammondia hammondi. A re-analysis of previous transcriptomic data indicated that ST gene expression is strongly linked to the adaptation to different situations such as extracellular passage (evolve and resequencing study) and changes in metabolism (lack of acetyl-CoA cofactor). In conclusion, the ST region of the T. gondii chromosomes was defined, the STs genes were determined, and it was possible to associate them with high interstrain plasticity and a role in the adaptability of T. gondii to environmental changes.

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Section: Resultsmentioning

confidence: 99%

Architecture, Chromatin and Gene Organization of Toxoplasma gondii Subtelomeres

et al. 2022

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“…2D, S3). Discrepancies between in vitro and in vivo settings have been highlighted in several studies describing the metabolic flexibility of T. gondii tachyzoites, which are able to scavenge a number of nutrients in rich culture medium but may encounter more restrictive conditions in the animal host (61). A number of host and parasite factors account for the heterogeneity in the ranges of mice brain cyst burden described in the literature, and while it is difficult to establish an exact correlation between the cyst burden and the initial inoculum, it is quite likely that a more successful acute phase can lead to increased parasite load in the brain (62, 63).…”

Section: Discussionmentioning

confidence: 99%

The apicoplast is important for the viability and persistence ofToxoplasma gondiibradyzoites

Sanchez

Bassot

Cerutti

et al. 2023

Preprint

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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, new specific therapeutic strategies targeting this developmental stage need to be discovered. 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 decrease in cyst burden or a loss of bradyzoite viability, highlighting the importance of this organelle for this developmental stage. This validates the apicoplast as a potential area to look for new therapeutic targets in bradyzoites, with the aim to interfere with this currently incurable parasite stage.

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“…Some specific Tgj1 interactors were already discussed above (mitochondria, membrane transport, and translocation), but the most notorious for their relevance to T. gondii , would be those associated with invasion/pathogenesis, cell shape, cell motility, and energy generation. T. gondii has a highly specialized machinery for cell motility/host cell invasion, and pathogenesis [ 48 , 49 , 50 ], and also shows significant flexibility in its metabolism and energy generation [ 51 , 52 ]. Studies on these subjects have emerged in recent years as they allow us to understand the parasite’s high capacity for adaptability to different environmental conditions.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Interactome of the Toxoplasma gondii Tgj1 HSP40 Chaperone

et al. 2023

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Toxoplasma gondii is an obligate intracellular apicomplexan that causes toxoplasmosis in humans and animals. Central to its dissemination and pathogenicity is the ability to rapidly divide in the tachyzoite stage and infect any type of nucleated cell. Adaptation to different cell contexts requires high plasticity in which heat shock proteins (Hsps) could play a fundamental role. Tgj1 is a type I Hsp40 of T. gondii, an ortholog of the DNAJA1 group, which is essential during the tachyzoite lytic cycle. Tgj1 consists of a J-domain, ZFD, and DNAJ_C domains with a CRQQ C-terminal motif, which is usually prone to lipidation. Tgj1 presented a mostly cytosolic subcellular localization overlapping partially with endoplasmic reticulum. Protein–protein Interaction (PPI) analysis showed that Tgj1 could be implicated in various biological pathways, mainly translation, protein folding, energy metabolism, membrane transport and protein translocation, invasion/pathogenesis, cell signaling, chromatin and transcription regulation, and cell redox homeostasis among others. The combination of Tgj1 and Hsp90 PPIs retrieved only 70 interactors linked to the Tgj1-Hsp90 axis, suggesting that Tgj1 would present specific functions in addition to those of the Hsp70/Hsp90 cycle, standing out invasion/pathogenesis, cell shape motility, and energy pathway. Within the Hsp70/Hsp90 cycle, translation-associated pathways, cell redox homeostasis, and protein folding were highly enriched in the Tgj1-Hsp90 axis. In conclusion, Tgj1 would interact with a wide range of proteins from different biological pathways, which could suggest a relevant role in them.

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Toxoplasma metabolic flexibility in different growth conditions

Cited by 19 publications

References 85 publications

Architecture, Chromatin and Gene Organization of Toxoplasma gondii Subtelomeres

Architecture, Chromatin and Gene Organization of Toxoplasma gondii Subtelomeres

The apicoplast is important for the viability and persistence ofToxoplasma gondiibradyzoites

Analysis of the Interactome of the Toxoplasma gondii Tgj1 HSP40 Chaperone

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