Investigating the molecular drivers of drug transport and resistance in Non-Tsetse Transmitted Animal Trypanosomes (NTTAT)

Surra is a wasting disease in equines, camels, and cattle caused by the animal pathogenic protozoan,

Trypanosoma evansi. It is non-specifically transmitted by biting insects and thus widely distributed geographically with an extensive range of mammalian hosts, resulting in a great economical loss. Dourine is a
venereal disease in horses and donkeys caused by Trypanosoma equiperdum.

Surra depends exclusively on chemotherapy, however, treatment is faced with the challenge of drug resistance. Dourine is considered incurable due to the parasites not responding to any of the available trypanocides.

Despite this global threat, worsened by the development of drug resistance, the mechanisms of resistance have hardly been investigated or understood.

While new surra/dourine drugs are urgently needed, understanding the mechanisms of drug resistance is as high a priority. Such fundamental knowledge is necessary for the rational design of new drugs that will not be cross-resistant with existing trypanocides.

Also, the identification of parasite-specific resistance genes would
enable us to develop a simple PCR-based identification test in the field. Doing that will prevent unsuccessful treatments and will ensure the development of better molecular tools to monitor drug resistance in the field, which will speed up disease elimination, ensuring that we have healthier animals.

Therefore, our aim in this Royal Society-funded research (RGS\R2\222269) is to find out which gene(s) is responsible for causing these parasites to resist the available drugs. We will use our knowledge of the biology of their close relative (T. brucei) to understand this by testing how the equivalent genes in NTTAT work in transporting trypanocides.