Fresh understanding of a cattle bug offers potential to design novel drug interventions for a devastating condition
21/07/2021 – Insights into a parasite that kills 3 million livestock each year could underpin the development of much-needed new treatments for infection.
Researchers have gained understanding of the parasite that causes animal African trypanosome (AAT) infection, the livestock equivalent of sleeping sickness.
Their study reveals key differences in the biology of the Trypanosome congolense parasite, which causes infection in animals, compared with the closely related T. brucei, which affects people.
These insights could pave the way for drugs to treat AAT and support further studies into the T. congolense parasite, which is spread by biting tsetse flies and largely affects cattle in sub-Saharan Africa.
Fresh understanding of the parasite’s behaviour could also help explain how drug resistance has become a significant problem in treating AAT. Novel therapies are urgently needed to treat infections, which have been managed by the same few drugs for decades.
The findings could also help shed light on how the parasite interacts with the animal’s immune system, further supporting efforts to manage infection.
A team of scientists including from the Roslin Institute, the Universities of Glasgow and Nottingham and industry partner GALVmed found key differences in how T. congolense and T. brucei interact with glucose and fatty acids in blood.
They also found variations in how each generates the key molecules they need to function in the bloodstream.
These insights offer potential for new drugs designed to interfere with these processes in T. congolense, to prevent it from perpetuating infection.
Researchers used data analysis to compare the genetic makeup of both parasites. They also studied how the parasites responded to tests interrupting key biological functions in each.
Their results highlight key departures in the characteristics of T. congolense compared with T. brucei, in how it produces the energy it needs to function and how it generates essential molecules needed to survive.
Their findings will inform the development of novel therapies for AAT and enable further research towards managing the disease.
The study, supported by the Biotechnology and Biological Sciences Research Council, part of UK Research and Innovation, and GALVmed, was published in PLOS Pathogens.
“The scale of animal African trypanosome infections is enormous, causing devastation to livestock, especially for cattle farmers. There are limited treatments available and drug resistance is a significant problem. This research forms a valuable resource for the T. congolense parasite, which we hope will underpin more research to target this important pathogen.” Prof Liam Morrison, The Roslin Institute.
“Technologies that enable detailed insights beyond the level of the genome of organisms are helping to build our knowledge base. For parasites such as T. congolense, this can have important implications in drug design and understanding drug resistance. Our study helps to dissect the differences between parasite species in detail, and will help to predict drug efficacy and interactions.” Dr Pieter Steketee, Research Fellow, the Roslin Institute.
“Trypanosomiasis is a major problem for livestock owners in Africa, Asia and Latin America. Developing new drug products is costly and it takes many years to develop and register safe and efficacious treatments. Understanding the metabolism of parasites such a trypanosomes helps researchers identify candidate molecules with the best chance of translation in to a successful treatment.” Michael Pearce, AAT Programme Manager, GALVmed.
** The Roslin Institute receives strategic investment funding from Biotechnology and Biological Sciences Research Council (BBSRC) and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies. **