Figure 9. A revised life cycle for the parasite Trypanosoma brucei.

Cell-cycle-arrested (G₀) metacyclic trypanosomes are injected by the tsetse fly into the mammalian host’s skin. There, the parasites re-enter the cell cycle, and proliferate as () slender forms in the blood, while disseminating into the interstitium and various tissues, including fat and brain. At least two triggers (SIF or ES) launch the PAD1-dependent differentiation pathway (light green boxes) to the cell cycle-arrested () stumpy bloodstream stage. Stumpy trypanosomes can establish a fly infection when taken up with the bloodmeal of a tsetse. The work described here reveals that proliferating slender stage trypanosomes are equally effective for tsetse transmission, that a single parasite suffices, and that the population can continuously divide while differentiating to the procyclic insect stage. The triggers that initiate further developmental transitions are temperature (°C), cis-aconitate (CA) and glucose deprivation (↓Glc).