The developmental trajectories of Toxoplasma stem from an elaborate epigenetic rewiring. Issue 1 (January 2022) - Farhat, Dayana C.
Abstract : Toxoplasma gondii is considered to be one of the most successful parasitic pathogens. It owes this success to its flexibility in responding to signals emanating from the different environments it encounters during its multihost life cycle. The adaptability of this unicellular organism relies on highly coordinated and evolutionarily optimized developmental abilities that allow it to adopt the forms best suited to the requirements of each environment. Here we discuss recent outstanding studies that have uncovered how master regulators epigenetically regulate the cryptic process of sexual development and the transition to chronicity. We also highlight the molecular and technical advances that allow the field to embark on a new journey of epigenetic reprogramming of T. gondii development. Highlights: Transcriptional and epigenetic programs in Toxoplasma gondii are established in a distinct developmental stage-specific manner. Through evolutionarily optimized adaptation to specific hosts, host-specific environments and metabolic states are critical for regulating the developmental pathways of the parasite. Applying technical innovations in stem-cell-based 3D culture systems as well as CRISPR-based assays, inducible knockdown, and single-cell transcriptomics to T. gondii is helping to uncover some of the hidden layers of its developmental processes. Hypotheses about master regulators in this organism are supported by the characterization of bradyzoite-formation-deficient 1 (BFD1) and microrchidia (MORC), which appear to operate at a relatively high level in the hierarchy of developmental pathways.