How does the pathogen colonize tsetse flies?

LMU researchers have deciphered an important signaling mechanism that enables trypanosomes to reach the salivary glands of flies.

Tsetse flies are spread throughout most of Africa. They feed on the blood of humans and other animals. In the process they can transmit trypanosomes, a protozoan parasite. Trypanosoma brucei It causes sleeping sickness in humans. The pathogens infiltrate the host through the saliva of the infected tsetse fly: from the blood it reaches the brain, leading to fatal symptoms if not treated.

But how do trypanosomes enter the salivary glands of tsetse flies after a blood meal? Dr. Sabine Bachmeyer and Professor Michael Buchart from the Department of Genetics at LMU’s School of Biology, along with scientific colleagues, have found a surprising answer to this question. They show that a signaling apparatus located at the flagellar tip of the incipient layer controls trypanosome migration in tsetse flies via a transmitter known as adenosine monophosphate (cAMP). Removal of a component of the enzyme complex that produces the cAMP signaling molecule was sufficient to prevent infection of the flies. The results of the study have now been published in Nature Communications.

Insight into the organizational network

For background: cattle and antelopes are natural reservoirs of Trypanosoma brucei. During a blood meal, pathogens enter the digestive tract of tsetse flies. In order to survive and reproduce, trypanosomes need to adapt to their changing environment. It migrates back and forth between the bloodstream and tissues of a mammalian host and between the digestive tract and salivary glands of the tsetse fly, where it passes through a series of developmental stages.

“Our project is based on several international collaborations with research groups in Paris, Antwerp and Rio de Janeiro,” says Bachmeier. “We have always been interested in the question of how parasites manage to orient themselves in the tsetse fly – and how this can be prevented in order to control disease transmission.”

About ten years ago, the research group identified a new trypanosome-specific component of the cAMP signaling pathway – AMP cyclic AMP response protein 3 (CARP3). “Our finding that CARP3 is located primarily at the tip of the trypanosome flagella puts us on the odor of a specialized signaling device to guide parasites in the tsetse fly,” says Bachmeier. When the researchers removed the CARP3 gene by genetic engineering, the make-up of the enzymes (adenylate cyclase) that produce cAMP at the tip of the flagellum also changed. “The trypanosomes are no longer able to efficiently colonize tsetse flies,” the scientist explains. “In the salivary glands, we don’t find a single parasite cell anymore.”

From basic research to application: The goal of the long-term strategy could be to weaken the interactions between CARP3 and adenylate cyclases. This can be done, for example, by a synthetic peptide that is produced in flies using the technique known as paratransgenesis. Without colonizing the salivary glands of tsetse flies, trypanosomes would not transmit anymore.

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Materials Introduction of Ludwig-Maximilians-Universit√§t M√ľnchen. Note: Content can be modified according to style and length.

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