Parasitologists from the University of Warwick, U.K., have succeeded in constructing a protein atlas for the infectious organism Trypanosoma brucei for the first time. This has been developed in order to understand the evolution of the parasite and to open up a gateway to developing more effective treatments, in the form of new drug targets.
The parasite can impose devastating impacts on agriculture and pose a risk to human health. The organism is the first pathogen to have its proteins located and then mapped within its cells. The insights from this offer some clues as to the function of the proteins.
T. brucei is found in sub-Saharan Africa. The organism lives in an extracellular environment, inhabiting blood plasma and body fluids. The parasites transmitted by tsetse flies (Glossina spp.) Both sexes of tsetse flies are blood feeders and equally transmit trypanosomes.
Once in the bloodstream, the parasitic organism causes the vector-borne disease African trypanosomiasis (sleeping sickness) in humans. First stage symptoms include headache, malaise, weakness, fatigue, pruritis, and arthralgia.
The complex T. brucei life cycle accounts for the difficulty in eradicating the disease. The parasite alternates between vector and host with multiple developmental forms and adaptations, including characteristic morphologies and specialized surface antigens.
The parasite also causes a similar disease called nagana in cattle. These parasites have made large areas of Africa unsuitable for livestock production. When an infected tsetse fly bites an animal, the parasites are transmitted through its saliva.
In drawing up the detailed “protein atlas” of the pathogen, researchers have gained an insight into understanding where proteins are within its cells. While both the cells of humans and T. brucei are eukaryotes (and hence possess a nucleus), T. brucei evolved in a different way.
According to Samuel Dean, assistant professor of parasitology: “In this study, we genetically modified trypanosome parasites to make proteins attached to a green fluorescent dye. This helped to show exactly where its proteins are within the cell. Using this information, we are able to understand more about what these proteins might be doing. Up until now 50 percent of the proteins in T. brucei had unknown functions.”
Dean continues: “This has significant impacts on our understanding of pathogen evolution and provides functional clues for thousands of otherwise uncharacterized proteins. This will help further investigations and may help to inform on new treatments for these terrible diseases.”
The research output provides an ongoing resource for researchers, including African scientists that work on African trypanosomiasis, assesses Lab Manager Magazine. This comes in the form of an enhanced understanding of the parasite biology.
The research appears in the journal Nature Microbiology, titled “Genome-wide subcellular protein map for the flagellate parasite Trypanosoma brucei.”
