Developmental gene expression in Eimeria bovis

Gubbels

Jerome

et al. 2004

Molecular Microbiology

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SummaryToxoplasma gondii sporozoites possess an array of stage-specific antigens that are localized to the membrane and internal cellular space, as well as secreted into the primary parasitophorous vacuole. Specific labelling of viable sporozoites excysted from oocysts reveals a complex admixture of surface proteins partially shared with tachyzoites. SAG1, SRS3 and SAG3 were detected on sporozoites as well as numerous minor antigens. In contrast, tachyzoite SAG2A and B were completely absent whereas a dominant 25 kDa protein was unique to the sporozoite surface. The sporozoite gene encoding this protein was identified in tachyzoites genetically complemented with a sporozoite cDNA library and cloned via site-specific recombination into a bacterial shuttle vector. The sporozoite cDNA identified in these experiments encoded a protein with conserved structural features of the prototypical T. gondii SAG1 (P30) and shared sequence identity with surface proteins from Sarcocystis spp. This new member of the SAG superfamily was designated SporoSAG. Expression of SporoSAG in tachyzoites conferred enhanced invasion on transgenic parasites suggesting a role for this protein in oocyst/sporozoite transmission to susceptible hosts.

Section: Discussionsupporting

confidence: 81%

Identification of a sporozoite‐specific member of the Toxoplasma SAG superfamily via genetic complementation

Gubbels

Jerome

et al. 2004

Molecular Microbiology

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“…This general theme also appears to fit our understanding of Apicomplexa development where changes in stage‐specific gene expression are reported to first appear in the cell division cycle immediately prior to developmental commitment. In Eimeria bovis , merozoite gene expression is detectable in fully sporulated sporozoites (Abrahamsen et al ., ) and in Plasmodium falciparum sexual stage commitment occurs in a subset of merozoites that will emerge from the erythrocyte as quiescent gametocytes (Bruce et al ., ). It is understood Toxoplasma tissue cyst formation requires replication (Bohne et al ., ), thus there is enrichment for S phase and mitotic parasites that characterizes the intermediate steps of bradyzoite development (Radke et al ., ), and basal expression of some bradyzoite mRNAs are detectable only in the S/M period of synchronized tachyzoites (Behnke et al ., ).…”

Section: Developmental Molecular Switchesmentioning

confidence: 99%

Toxoplasmadevelopment - turn the switch on or off?

White

2014

Cell Microbiol

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SummaryToxoplasma gondii exhibits a complex, multi-stage life cycle in which the need for parasite expansion is balanced with the production of transmissible forms. For human disease the key developmental switch is from the tachyzoite to the mature bradyzoite, which is not well understood at the molecular level. This review highlights the role of the tachyzoite in regulating the initiation of bradyzoite differentiation through newly discovered transcription factors of the ApiAP2 family that must be turned off for development to unfold. Exit from the tachyzoite cell cycle is also tightly co-ordinated with the induction of bradyzoite gene expression, which is strongly influenced by the host cell environment. New evidence suggests a parasite casein kinase II and host anti-growth factor CDA1 can influence specific pathways that are responsible for sensing the host cell environment and informing the parasites decision to continue replication or to develop into bradyzoites. These results indicate tachyzoite gene expression mechanisms and signal transduction pathways likely hold the keys to tissue cyst formation in Toxoplasma.

“…Similar ApiAP2 expression profiles in tachyzoites and bradyzoites was expect because the transcriptomes of these stages are highly correlated (17,18). Common ApiAP2 expression between the intermediate life cycle and oocyst stages was also anticipated as more than 20 years ago we established the principal that coccidian sporozoites are pre-programmed for the next stage of development (19), which in Toxoplasma is the tachyzoite .…”

Section: Ap2iv-3 Is One Of Five Apiap2 Factors Expressed Early In Bramentioning

confidence: 81%

Opposing transcriptional mechanisms regulateToxoplasmadevelopment

Hong

White

2016

Preprint

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The Toxoplasma biology that underlies human chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite stage. We investigated the roles of two alkaline-stress-induced ApiAP2 transcription factors, AP2IV-3 and AP2IX-9, in bradyzoite development. These factors were expressed in two overlapping waves during bradyzoite development, with AP2IX-9 increasing expression earlier than AP2IV-3, which peaked as AP2IX-9 expression was declining. Disruption of the AP2IX-9 gene enhanced, while deletion of AP2IV-3 gene decreased, tissue cyst formation, demonstrating that these factors have opposite functions in bradyzoite development. Conversely, conditional overexpression of FKBP-modified AP2IX-9 or AP2IV-3 with the small molecule Shield 1 had a reciprocal effect on tissue cyst formation, confirming the conclusions of the knockout experiments. The AP2IX-9 repressor and AP2IV-3 activator tissue cyst phenotypes were borne out in gene expression studies that determined that many of the same bradyzoite genes were regulated in an opposite manner by these transcription factors. A common gene target was the canonical bradyzoite marker BAG1, and mechanistic experiments determined that, like AP2IX-9, AP2IV-3 regulates a BAG1 promoter-luciferase reporter and specifically binds the BAG1 promoter in parasite chromatin. Altogether, these results suggest that the AP2IX-9 transcriptional repressor and the AP2IV-3 transcriptional activator likely compete to control bradyzoite gene expression, which may permit Toxoplasma to better adapt to different tissue environments and select a suitable host cell for long-term survival of the dormant tissue cyst.IMPORTANCE Toxoplasma infections are lifelong because of the development of the bradyzoite tissue cyst, which is effectively invisible to the immune system. Despite the important clinical consequences of this developmental pathway, the molecular basis of the switch mechanisms that control tissue cyst formation is still poorly understood. Significant changes in gene expression are associated with tissue cyst development, and ApiAP2 transcription factors are an important mechanism regulating this developmental transcriptome. However, the molecular composition of these ApiAP2 complexes and the operating principles of ApiAP2 mechanisms are not well defined. Here we establish that competing ApiAP2 transcriptional mechanisms operate to regulate this clinically important developmental pathway.