A group of micro-organisms called kinoplasts contain the parasites that cause terrible diseases such as sleeping sickness in Africa, Chagas disease, and leishmaniasis. They share the ability to adhere to the sides of their insect host, using a specific protein structure. But what would happen if scientists could prevent the parasite from complying with it? Would the parasites come through the vectors, if they could not pass them on to someone?
This is the idea behind a new study led by Michael Povelones from the School of Veterinary Medicine Penn and Megan L. Povelones from Penn State Brandywine. It is caused by non-disease kinetoplastid species Crithidia fasciculataThis husband duo and his research team identified some genes that were involved with their mosquito host.
“The parasite must be running so it won't go through,” says Michael Povelones, assistant professor of pediology at Penn Vet. “It must be kept in the stomach to eventually be transmitted and transmitted. It seems that these mechanisms comply [shared] around kinetoplastid species, so we hope that we have an insight into Crithidia he will tell us something about adherence to the medically relevant species. ”
The study is available in the magazine Tropical Diseases PLOS are neglected.
Scientists have gone a long way Crithidia fasciculata as a biochemical model for understanding elements of parasitic disease, as it grows easily in the laboratory. Megan Povelones, who specializes in trypanosomiasis in Africa, was familiar with her doctoral studies at Johns Hopkins University, and the material came together in conversations with her husband.
“We sometimes speak a home shop,” says Michael Povelones, who focused his own research on ways to empower the mosquito's own immune protections to prevent them from transmitting disease. “I was surprised that Crithidia mosquitoes infects but it is not an animal or animal pathogen, there was little information about its life cycle, and that some electronic microscope studies were carried out showing that the parasite is adhering to the mosquito lock with a very specific type of structure described by humans. as hemidesmosome. I felt there was some great cell biology there to explore. ”
Together they decided to inquire what happens to enable the parasite “bite to keep” the inside of the mosquito, a characteristic believed to be vital for disease transmission.
In the laboratory, the researchers were able to replicate what other scientists had previously received: t Crithidia the two bathing forms contain parasites, with a similar character called flagellum, and a paste form, which adheres to the surface of the plastic dishes in which they are grown in the laboratory. The bathing form preferred when the cultural dishes were placed on a crofter, and it was more likely that the adhesive form, which was divided into rosette structures, developed when the dishes were kept at rest. It is notable that they noted that the sticky parasites in the roses would occasionally give rise to bathing versions.
To focus on the adhesive parasites, the researchers would wait to see rosettes and then wash the bath parasite away. They could then focus on investigating the genetics of both types.
“One question we had was very simple,” said Michael Povelones, “yes,‘ What are the differences in transcription between the swimming cells compared to those allowed to grow as rosettes. '”
Impressively, for two species of the same species growing in the same medium, the researchers found a significant amount of variation in gene expression between the two.
“The adhesion process changed their transcription in a very dramatic way,” said Michael Povelones.
When the researchers put an infection on a laboratory mosquito song Crithidia, they discovered that the parasites that had complied with the mosquitoes, particularly in their own region, were similar to the adhesive form they were working in the lab, which gave them confidence that they might study them. lab-song important information about what was happening in the host parasites insects.
Improved expression genes included a group called GP63s associated with adhesion to immune cells in the Gaeltacht. Leishmania parasite.
The team expects further investigations into adhesion Crithidia as a tool, looking specifically at genes involved in the process it is known that they are divided across kinetoplastid species and may be a target day to prevent the transmission of vector-borne diseases.
Michael and Megan Povelones collaborated with the study by John N. Filosa Penn, an undergraduate researcher in Michael Povelones laboratory; Corbett T. Berry, Penn Vet and Gordon Ruthel; Stephen M. Beverley and Chad Tomlinson from Washington University in St. Louis; Wesley C. Warren, University of Missouri; Peter J. Myler, University of Washington; and Elizabeth A. Dudkin of State State Brandywine.
The study was supported by the National Science Foundation (Grant 1651517) and the National Institutes of Health (grants OD021633-01, AI29646, HG00307907, and AI103858).