Sleeping sickness mechanism observed

African sleeping sickness
Photo by Karen Tian.

Researchers now understand how Trypanosoma brucei, the parasite responsible for African sleeping sickness, becomes infectious.

Scientists from the Yale School of Public Health, Yale School of Medicine and The Rockefeller University are the first to mimic the natural development of infectivity — the parasite’s ability to cause infection — in a laboratory setting. Infectious forms of T. brucei inside the tsetse fly can infect humans and cause African sleeping sickness, also known as African trypanosomiasis. Researchers identified a protein that triggers the infection in healthy cells, which could provide new intervention strategies in blocking progression of the disease, said study co-author Christian Tschudi, a professor of epidemiology and director of graduate studies at the Yale School of Public Health. The research findings were published in the Dec. 7 edition of Science.

“I think it’s a major breakthrough,” said researcher Serap Aksoy, professor of epidemiology of microbial diseases at the Yale School of Public Health.

In the past, scientists only observed the life cycle of infectious T. brucei parasites within the tsetse fly vector responsible for transmitting African sleeping sickness. The study’s researchers sequenced the RNA of T. brucei parasites from infected tsetse fly tissues to determine the mechanisms that cause infectivity. The results indicated that high levels of the protein RBP6 occurred during a critical development stage of the parasite. Once researchers had discovered high levels of RBP6 in infected tsetse flies, they artificially raised expression of the protein in healthy T. brucei cells that had not been exposed to flies. They found that these healthy cells suddenly became infectious.

“We had no idea this would happen,” said Tschudi. “This was completely serendipitous.”

The protein is now seen as the initial trigger in the cascade of events causing the infectious form of the parasite.

Jayne Raper, professor of biological sciences at Hunter College of the City University of New York, described the findings as a “holy grail” to the field. She said the ability to induce infectivity in T. brucei without an accompanying fly vector “now gives a huge area of research that people can embark upon.”

Though African sleeping sickness affects thousands of people in sub-Saharan Africa, relatively little was known about the precise mechanisms of the parasite’s development within the tsetse fly prior to this study, said first author Nikolay Kolev, associate research scientist at the School of Public Health. Since the infectious forms of the parasite could previously only be observed in the flies, developing effective medications proved difficult. While there are several medicines that work against the disease, such drugs are “horrible” and “extremely hard to administer,” Tschudi said.

Sleeping sickness is found in 36 sub-Saharan African countries.

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