Forward genetics in Toxoplasma gondii reveals a family of rhoptry kinases that mediates pathogenesis. Review 50 refs

摘要

Toxoplasma gondii is a widespread protozoan parasite that commonly infects domestic, wild, and companion animals (8). Like related tissue coccidians, T. gondii has a complex life cycle alternating between a sexual cycle, which occurs only within enterocytes of the small intestines of cats (all members of the Felidae appear to be susceptible), and asexual propagation in a variety of warm-blooded vertebrate hosts (8). The sexual phase culminates with fecal shedding of a spore-like stage called the oocyst, which is diploid and undergoes meiosis in the environment. During the asexual cycle, the parasite interconverts between a fast-growing lytic form known as the tacyhzoite and a slow-growing, semidormant form called the bradyzoite. Tachyzoites propagate rapidly in virtually all types of nucleated cells, including macrophages, while differentiation to bradyzoites is favored in long-lived, terminally differentiated host cells (49). Tachyzoites are adept at direct migration across cellular barriers and also disseminate rapidly within leukocytes, thereby reaching sites of immune privilege such as the central nervous system and the developing fetus, where they are more likely to cause disease (2). The life cycle shows remarkable flexibility between lytic and dormant states, thus facilitating asexual transmission between intermediate hosts. This adaptation may account for the recent spread and emergence of a few dominant clonal groups within North America and Europe (46).