Toxoplasmadevelopment - turn the switch on or off?

Abstract

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.

A Novel Bipartite Centrosome Coordinates the Apicomplexan Cell Cycle

“…The development of specialized invasion and replication strategies [3–5] has permitted these parasites to surmount a variety of host-defensive barriers and achieve sufficient expansion in many different host tissues. Apicomplexan replication has adapted to different host cells, most commonly using a sequence of two chromosome replication cycles uniquely regulated in different parasite genetic lineages [4].…”

Translational Control in the Latency of Apicomplexan Parasites

“…These parasites have a well-developed capacity to sense changes to their environment and employ an ISR to initiate rapid adaptive changes that can include progression to a latent state. Multiple layers of gene regulation are involved in the switch from proliferative to dormant stages, including important epigenetic and transcriptional effects that have been extensively reviewed [1,2,105,106]. The eIF2 kinases provide a mechanism to not only sense environmental insults, but initiate preferential translation that leads to the reprogramming of gene expression required for latency.…”

“…A transcriptional response was also induced upon ER stress in tachyzoites that included the induction of genes that encode bradyzoite surface antigens, putative transcription factors, and RNA regulatory proteins such as the RNA-binding protein PUF1, which likely has a role in translational repression [50,54]. Since epigenetic remodeling and changes in gene transcriptional regimens are known to be important for bradyzoite development and stage switching towards latency in general, these translational and transcriptional responses support the idea that the sensing of stress mediated through eIF2 phosphorylation can drive parasite differentiation [1,2,55]. …”

“…Determining the gene regulatory mechanisms involved in the maintenance of latency and the conversion to replicative stages after transmission may also reveal exploitable strategies to control these parasites. While epigenetic and transcriptional gene regulatory regimens are crucial driving forces of parasite differentiation [1,2], recent findings indicate that post-transcriptional gene regulation also plays an important role in these processes. Here, we discuss an emerging paradigm in which the control of protein synthesis is essential for the initiation, maintenance, and relief of parasite latency.…”

“…In Apicomplexa, transcription is regulated by factors containing a plant-like DNA-binding domain known as AP2 [1,62]. In Plasmodium , AP2 factors have been shown to regulate stage-specific gene expression required for life cycle stage differentiation [63–69].…”