T. brucei splits its life cycle between two hosts: a mammal such as a human or a cow, and a tsetse fly. The mammal-dwelling form multiplies in the bloodstream and spreads throughout the brain and other organs. When a tsetse fly bites an infected mammal to get a blood meal, it sucks up the parasite as well. The trypanosome divides in the insect gut, then makes its way into the bug’s saliva, ready to hitch a ride to a new mammalian host when the fly gets its next meal.
The two hosts present very different physical living environments. Imagine being suddenly sucked from a host in the American Southeast and spat out into the Arctic tundra. Different surroundings, different climates, different strategies needed for survival. But this parasite has evolved to adapt to the abrupt shift by assuming different forms tailored for each host.
One crucial environmental difference is blood sugar. Mammals have a relatively high level of glucose in their blood; tsetse flies have almost none. And sugar equals energy. Glucose is the primary energy source for the mammal-dwelling form of the parasite. When the trypanosome is slurped into the fly gut, the sudden absence of sugar is what triggers a quick switch into its insect-adapted form, which dines on a diet of bug amino acids instead.
It’s an impressive evolutionary adaptation. But what’s more, it’s an opportunity the researchers can exploit, Morris says. If, in a mammal, the researchers can find a way to make the parasite think it’s in an insect, they may be able to trick it into assuming the wrong form — and dying. A compound that can accomplish that in an infected person has the makings of a powerful treatment, he reasons.
“If you block glucose uptake, the parasite might perceive that as, ‘Hey, there’s no glucose around!’ and then fire off the developmental program to assume the insect stage in the blood, which would be very bad for the parasite,” Morris explains. “So it’s a win-win: You either starve them … or you force them to become a stage that can’t live in the mammal.”
This has become a cornerstone of his research program: targeting T. brucei’s ability to access glucose, in search of a new kind of anti-parasite treatment.