Toxoplasma Transcription Factor TgAP2XI-5 Regulates the Expression of Genes Involved in Parasite Virulence and Host Invasion

Walker, Robert B.; Gissot, Mathieu; Huot, Ludovic; Alayi, Tchilabalo Dilezitoko; Hot, David; Marot, Guillemette; Schaeffer-Reiss, Christine; Dorsselaer, Alain Van; Kim, Kami; Tomavo, Stanislas

doi:10.1074/jbc.m113.486589

Cited by 41 publications

(55 citation statements)

References 27 publications

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“…gondii genome. Some of these are cell-cycle-regulated [65] and have been implicated in the transcriptional regulation of interconversion of tachyzoites to bradyzoites [66,67] and of virulence determinants, including ROP18 [68]. Six genes encoding AP2-domain transcription factors had higher expression in sporozoites relative to tachyzoites, including TgAP2X-2 with an ~4-fold increase, whereas 17 such genes were significantly lower in the sporozoites (Table 12).…”

Section: Resultsmentioning

confidence: 99%

An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells

et al. 2017

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Toxoplasmosis is a zoonotic infection affecting approximately 30% of the world’s human population. After sexual reproduction in the definitive feline host, Toxoplasma oocysts, each containing 8 sporozoites, are shed into the environment where they can go on to infect humans and other warm-blooded intermediate hosts. Here, we use an in vitro model to assess host transcriptomic changes that occur in the earliest stages of such infections. We show that infection of rat intestinal epithelial cells with mature sporozoites primarily results in higher expression of genes associated with Tumor Necrosis Factor alpha (TNFα) signaling via NF-κB. Furthermore, we find that, consistent with their biology, these mature, invaded sporozoites display a transcriptome intermediate between the previously reported day 10 oocysts and that of their tachyzoite counterparts. Thus, this study uncovers novel host and pathogen factors that may be critical for the establishment of a successful intracellular niche following sporozoite-initiated infection.

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Section: Resultsmentioning

confidence: 99%

An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells

et al. 2017

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“…Similarly to their plant counterparts, ApiAP2 proteins function as transcriptional regulators throughout all stages of parasite development. To date, seven ApiAP2 proteins have been identified as regulators of stage-specific development, including liver-stage maturation (AP2-L) 71 , salivary gland sporozoite formation (AP2-Sp) 73 , ookinete development (AP2-O) 72 and gametocyte commitment (AP2-G) 47,50 in Plasmodium spp., as well as bradyzoite development (AP2IX-9 and AP2XI-4) 125,126 , virulence and host invasion (AP2XI-5) in the related apicomplexan parasite Toxoplasma gondii 127 . Many ApiAP2 proteins are also predicted to be involved in the regulation of the parasite cell cycle 75,[128][129][130][131] .…”

Section: Box 2 | Apiap2 Dna-binding Proteinsmentioning

confidence: 99%

Sexual development in Plasmodium parasites: knowing when it's time to commit

2015

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Malaria is a devastating infectious disease that is caused by blood-borne apicomplexan parasites of the genus Plasmodium. These pathogens have a complex lifecycle, which includes development in the anopheline mosquito vector and in the liver and red blood cells of mammalian hosts, a process which takes days to weeks, depending on the Plasmodium species. Productive transmission between the mammalian host and the mosquito requires transitioning between asexual and sexual forms of the parasite. Blood- stage parasites replicate cyclically and are mostly asexual, although a small fraction of these convert into male and female sexual forms (gametocytes) in each reproductive cycle. Despite many years of investigation, the molecular processes that elicit sexual differentiation have remained largely unknown. In this Review, we highlight several important recent discoveries that have identified epigenetic factors and specific transcriptional regulators of gametocyte commitment and development, providing crucial insights into this obligate cellular differentiation process.

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“…(37) characterized the binding motifs for all 27 members of the ApiAP2 family in P. falciparum and used these data in conjunction with intra-erythrocytic expression data to predict putative regulatory targets of these proteins (37). The role of ApiAP2 proteins in gene regulation has also been investigated to a lesser degree in T. gondii , where several ApiAP2 proteins have been implicated in regulating progression through the cell cycle (38) as well as crucial virulence factors (14). Other studies have implicated ApiAP2s in regulating a developmental transition (13).…”

Section: Introductionmentioning

confidence: 99%

TheCryptosporidium parvumApiAP2 gene family: insights into the evolution of apicomplexan AP2 regulatory systems

et al. 2014

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We provide the first comprehensive analysis of any transcription factor family in Cryptosporidium, a basal-branching apicomplexan that is the second leading cause of infant diarrhea globally. AP2 domain-containing proteins have evolved to be the major regulatory family in the phylum to the exclusion of canonical regulators. We show that apicomplexan and perkinsid AP2 domains cluster distinctly from other chromalveolate AP2s. Protein-binding specificity assays of C. parvum AP2 domains combined with motif conservation upstream of co-regulated gene clusters allowed the construction of putative AP2 regulons across the in vitro life cycle. Orthologous Apicomplexan AP2 (ApiAP2) expression has been rearranged relative to the malaria parasite P. falciparum, suggesting ApiAP2 network rewiring during evolution. C. hominis orthologs of putative C. parvum ApiAP2 proteins and target genes show greater than average variation. C. parvum AP2 domains display reduced binding diversity relative to P. falciparum, with multiple domains binding the 5′-TGCAT-3′, 5′-CACACA-3′ and G-box motifs (5′-G[T/C]GGGG-3′). Many overrepresented motifs in C. parvum upstream regions are not AP2 binding motifs. We propose that C. parvum is less reliant on ApiAP2 regulators in part because it utilizes E2F/DP1 transcription factors. C. parvum may provide clues to the ancestral state of apicomplexan transcriptional regulation, pre-AP2 domination.

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Toxoplasma Transcription Factor TgAP2XI-5 Regulates the Expression of Genes Involved in Parasite Virulence and Host Invasion

Cited by 41 publications

References 27 publications

An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells

An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells

Sexual development in Plasmodium parasites: knowing when it's time to commit

TheCryptosporidium parvumApiAP2 gene family: insights into the evolution of apicomplexan AP2 regulatory systems

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