Fig 1.
Nonreplicating Toxoplasma uracil auxotrophs (NRTUAs) do not replicate in living host animals.
Left panel: Toxoplasma NRTUAs invade host cells in vitro and replicate normally if the nutrient uracil is added to the culture medium. Center panel: Toxoplasma NRTUAs invade host cells in vitro but do not replicate in the absence of uracil supplementation. Right panel: Mammalian hosts have extremely low uracil concentrations because they do not express the uracil phosphoribosyltransferase enzyme, and therefore, pyrimidine salvage instead occurs through nucleoside kinases that salvage the nucleoside uridine into uridine 5′-monophosphate (UMP) [17]. In living hosts, Toxoplasma NRTUAs invade host cells but do not replicate because there is insufficient uracil to support replication.
Fig 2.
Toxoplasma is a bottle-shaped eukaryotic microbe that uses specialized secretory organelles to invade the host cell, to establish a parasitophorous vacuole, and to manipulate host signaling and transcriptional pathways.
Top-left panel: Toxoplasma secretory organelles. Top-right panel: 14 events that occur during invasion of the host cell to establish the parasitophorous vacuole habitat as well as manipulation of the host cell (adapted from reference [16]). The displayed order of these invasion steps should be interpreted cautiously at this time since the elucidation of the precise order of some of these steps and the mechanisms regulating gliding motility, invasion, and secretion events are major topics of ongoing research into the biology of Toxoplasma [16, 29, 32]. Bottom panel: An expanded view of an NRTUA-invaded cell shows the host cell localization of Toxoplasma secreted effectors necessary to trigger an antitumor response. See the main text for explanations. Abbreviations: GRA, protein secreted from the dense granules; IVN, intravacuolar network; MIC, microneme adhesin or other microneme secreted protein; NM, nuclear membrane of the host cell; NRTUA, nonreplicating Toxoplasma uracil auxotroph; PM, plasma membrane of the host cell; PVM, parasitophorous vacuole membrane; PV space, parasitophorous vacuole space; RON, rhoptry neck secreted protein; ROP, rhoptry bulb secreted protein.