Mechanisms ofToxoplasma gondiipersistence and latency

Abstract

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes opportunistic disease, particularly in immunocompromised individuals. Central to its transmission and pathogenesis is the ability of the proliferative stage (tachyzoite) to convert into latent tissue cysts (bradyzoites). Encystment allows Toxoplasma to persist in the host, and affords the parasite a unique opportunity to spread to new hosts without proceeding through its sexual stage, which is restricted to felids. Bradyzoite tissue cysts can cause reactivated toxoplasmosis if host immunity becomes impaired. A greater understanding of the molecular mechanisms orchestrating bradyzoite development is needed to better manage the disease. Here we will review key studies that have contributed to our knowledge about this persistent form of the parasite and how to study it, with a focus on how cellular stress can signal for the reprogramming of gene expression needed during bradyzoite development.

Discovery of Potent and Selective Leads against Toxoplasma gondii Dihydrofolate Reductase via Structure-Based Design

“…1 Cysts have the propensity to populate within longer lived tissue types, particularly those of the brain, eye, and skeletal muscle. 10,11 Rupture of tissue cysts releases the encapsulated parasite, leading to re-emergence of acute infection. Acute toxoplasmosis can cause severe illness, particularly in immunocompromised patients for whom the disease can be life threatening.…”

Phosphatidylethanolamine Synthesis in the Parasite Mitochondrion Is Required for Efficient Growth but Dispensable for Survival of Toxoplasma gondii

“…), tachyzoites convert into bradyzoite-containing cysts (chronic infection) (2). Such cysts are commonly formed in the neural and muscular tissues and persist for the entire life of the infected host (2).…”

“…The rapid replication of intracellular tachyzoites and concomitant expansion of the parasitophorous vacuole are accompanied by significant membrane synthesis and nutritional import from the host cell (3). Similar to other eukaryotes, phospholipids account for a major fraction of parasite membranes, which include phosphatidylcholine (PtdCho), 2 PtdEtn, phosphatidylinositol, and PtdSer (4). T. gondii has the potential to synthesize its major phospholipids (4 -6) and harbors a relatively complete set of enzymes for de novo synthesis (4,5).…”

Elongator Protein 3 (Elp3) Lysine Acetyltransferase Is a Tail-anchored Mitochondrial Protein in Toxoplasma gondii

“…Toxoplasma is an obligate, intracellular protozoan in the phylum Apicomplexa and causes life-threatening opportunistic infection in immunocompromised individuals (11). The parasite can also be transmitted vertically to the fetus of a woman infected for the first time during pregnancy, resulting in spontaneous abortion or birth defects.…”