LSTM’s seminar series: Dyskinetoplastic trypanosomes – how to put tsetse flies and a few hundred mitochondrial proteins out of business

News article 28 Nov 2013

LSTM’s seminar series continued today with a presentation by Dr Achim Schnaufer of the Institute for Immunology and Infection, University of Edinburgh.  The presentation, entitled “Dyskinetoplastic trypanosomes – how to put tsetse flies and a few hundred mitochondrial proteins out of business” was introduced by LSTM’s Dr Alvaro Acosta-Serrano.

Dr Schnaufer started with the example point for his work of Waud, a horse in Sicily who, during a batch of tests, showed positive for sexually transmitted disease Dourine, last diagnosed in 30 years ago. The trypanosome species responsible - Trypanosoma equiperdum is so similar to T. brucei, carried by tsetse flies and exclusively found in sub-Saharan Africa, that the question was posed as to how it had managed to get out of Africa.

He then described the standard life cycle of T. brucei, the forms that it takes in mammalian blood, how it adapts to life in the tsetse fly, and the changes undertaken within the insect host in preparation to be reintroduced into the mammal again via a bite. He described the adaptations of T. equiperdum and T. evansi to tsetse independent transmission mammal to mammal, reducing its life cycle and allowing it to travel from Africa.

The shortening of the life cycle in these trypanosomes coincides with becoming independent from, and loss of, mitochondrial DNA, (the ‘kinetoplast’ in trypanosomes), leading to more or less completely dyskinetoplastic forms. He described work that he had carried out along with colleagues to identify the mutations that had allowed these trypanosomes to survive without mitochondrial DNA, and how mutated ATPase had become necessary and sufficient to compensate for the loss of it.

He demonstrated the utility of kinetoplast-independent cell lines for the identification of genes important for kinetoplast maintenance and expression.

He went on to look at the implications that this may have in relation to the drugs used to treat the diseases caused by trypanosomes, and whether or not the mode of action for those drugs is in any way related to their effect on mitochondrial DNA. While he found that some drugs were less effective with the mutated strains, others showed no difference in sensitivity at all.

He concluded by confirming that T. equiperdum and T.evansi have evolved from T. brucei on at least four different occasions.