Preventing parasites from adhering to the intestines of mosquitoes could prevent the transmission of the disease

A group of microorganisms called kinetoplasties includes parasites that cause devastating diseases such as African sleeping sickness, Chagas disease and leishmaniasis. They share an ability to adhere to their host insects, using a specialized protein structure. But if scientists could prevent the parasite from joining? Would the parasites pbad through the vectors, without being able to be transmitted to a human?

This is the idea of ​​a new study led by Michael Povelones of the Penn Veterinary School and Penn State's Megan L. Povelones Brandywine. Using a species of kinetoplastide that does not cause disease, Crithidia fasciculata, this husband-wife duo and her research team have identified a number of genes involved in adhesion in her mosquito host.

The parasite must hold on to not get through. It must be retained in the intestine to multiply and possibly be transmitted. These adhesion mechanisms seem to be [shared] We hope that our knowledge of Crithidia will provide information on compliance with species of medical interest. "

Michael Povelones, Assistant Professor of Pathobiology, Penn Vet

The study appears in the newspaper PLOS Neglected Tropical Diseases.

Scientists have long since turned to Crithidia fasciculata as a biochemical model to understand the characteristics of the parasitic disease, as it is easily cultivated in the laboratory. Megan Povelones, whose specialty is African trypanosomiasis, had already known her since her doctoral studies at Johns Hopkins University, and the subject was discussed in conversations with his wife.

"We sometimes talk at home," says Michael Povelones, whose research has focused on ways to harness the power of the mosquito's immune defenses to prevent it from transmitting disease. "I am intrigued by the fact that Crithidia infects mosquitoes but is not a human or animal pathogen, that its life cycle is poorly known and that electron microscopic studies have been conducted to show that the parasite was adhering to actually to the gut mosquito with a very specific type of structure that people had described as a hemidesmosome.I thought that there was there a fascinating cell biology to explore. "

Together, they set out to study what allows the parasite to "hang" inside the mosquito, a trait considered essential for the transmission of the disease.

In the lab, the researchers were able to replicate what other scientists had previously discovered: Crithidia parasites exist both in a swimming form, with a tail-shaped appendage called flagellum, and an adherent form that even adheres to the surface of the plastic dishes in which they were grown in the laboratory. The swimming shape was favored when the culture dishes were placed on a shaker, while the adherent shape, which split to form rosette structures, was more likely to develop when the dishes were kept motionless. Interestingly, they observed that adherent parasites in rosettes sometimes gave rise to swimming versions.

To focus on adherent parasites, researchers would wait for rosettes to appear and then eliminate the parasite swimmer. They could then focus on genetic research of both types.

"One of the questions we had was very simple," says Michael Povelones, "What were the transcription differences between the swimming cells compared to those allowed to grow in rosettes?"

Remarkably, for two forms of the same species growing in the same medium, the researchers found a significant variation in gene expression between the two.

"The membership process has transformed their transcriptome dramatically," says Michael Povelones.

When the researchers infected laboratory strains of mosquitoes with Crithidia, they found that mosquito-adherent parasites, mainly in the posterior gut region, resembled the adherent form they grew in the laboratory, which gave them the certainty that the study of laboratory strains could reveal important information about what was happening in insect hosts of parasites.

Among the genes with improved expression, there is a group called GP63, involved in adhesion to the immune cells of the Leishmania parasite.

The team hopes to continue its research on adhesion using Crithidia as a tool, by looking more specifically at the genes involved in the process that are known to be shared by kinetoplastid species and that could perhaps one day serve as targets for block the transmission of vector-borne viruses. diseases.