Interactions of trypanosomatid Herpetomonas muscarum with dipteran Drosophila melanogaster

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). With resistance to both vector-targeted pesticides and trypanocidal drugs being reported, there is a need for novel transmission blocking strategies to be developed. Studies using the blood-feeding vectors themselves are not broadly accessible, as such, new model systems are being developed to unpick insect-trypanosmatids interactions. In this thesis the interactions between model dipteran Drosophila melanogaster and its own natural trypanosomatid Herpetomonas muscarum are investigated from the perspective of the parasite. This work describes the sequencing and annotation of the H. muscarum genome, which was shown to be highly syntenic to disease-causing trypanosomatids, especially with those of the Leishmania genus. Infections of D. melanogaster were shown to be confined to adults, where H. muscarum persisted in the crop and midgut of the flies for 3-4 days. RNA-sequencing analysis of infected flies showed that rapid, large-scale transcriptomic changes, associated with autophagy, nutrient acquisition and cell surface remodelling, are triggered in H. muscarum after ingestion by the fly. Much of the transcriptomic changes observed reflect what is known for disease-causing trypanosomatids. As such, several of the identified surface proteins are of interest as putative transmission blocking targets. Further characterisation of these genes will be greatly aided by genetic manipulation methods developed for H. muscarum as part of this work. This thesis has described multiple, evolutionarily conserved, trypanosomatid responses to ingestion by dipterans by using a Drosophila-Herpetomonas model. Future studies of these conserved responses will inform development of novel, broad-spectrum transmission blocking strategies.