The genetic basis of host specificity in African trypanosomes: why do some species prefer pigs?

Animal African Trypanosomiasis (AAT) is a disease that places a major burden on livestock farming in sub-Saharan Africa, with impacts on sustainable food production and food security, as well as animal health. The disease is caused by microscopic single-celled parasites (trypanosomes) found in the blood of infected animals and spread by bloodsucking tsetse flies. AAT affects cattle, as well as a range of other animals including pigs, sheep and goats. There is no vaccine against AAT and new drugs are urgently needed to counter increasing resistance to current drugs. AAT has held back development in many African countries, as it severely constrains agricultural productivity through its harmful effects on livestock production and draught animals, with impacts on people's wealth, livelihoods and health. Climate change is likely to exacerbate the impact of AAT through changes in tsetse fly distribution altering the transmission dynamics of the disease.
While there has been a major push to eliminate human African trypanosomiasis or sleeping sickness in recent years, research on the parasites that cause AAT, the equivalent livestock disease, has lacked impetus. Several trypanosome species cause AAT and the host range includes both wild and domestic animals, making it a complex disease to combat. Among these trypanosomes, some have a wide host range including cattle, small ruminants and pigs, while others are restricted to pigs. The underlying reasons for restriction to certain livestock hosts are unknown. Here we will investigate whether host specificity has a genetic basis by looking at how pig-restricted trypanosomes originated and diverged over time from those with a broader host range. We will take advantage of recent advances in gene sequencing technology to obtain the complete set of genes - the genome - from each trypanosome. At Bristol, we have a unique collection of trypanosomes isolated over many years of fieldwork in sub-Saharan Africa, which we will use to extract purified DNA for genome sequencing. Each genome will be carefully assembled, allowing us to compare variation in the sequence and numbers of individual genes between trypanosomes. For example, we will be able to determine whether certain genes or variants are associated with adaptation to pig hosts. Not only will this allow us to test hypotheses on how host specificity evolved, but also make predictions about the probability of host switches in the future. The new trypanosome genome sequences we will obtain will also serve as an essential resource for future work on these important parasites, including drug development. Research into AAT is often focused on cattle to the exclusion of other livestock, but pigs and small ruminants also suffer from AAT and these livestock are becoming increasingly important to smallholders as sources of food and wealth. The control of AAT is thus an important task in terms of increasing food production and supply in sub-Saharan Africa, thereby progressing global development goals in sustainable agriculture and food security.

Animal African Trypanosomiasis (AAT) places a major burden on livestock health, sustainable food production and food security in sub-Saharan Africa. The disease is caused by trypanosomes, protozoan parasites found in the blood of affected livestock and transmitted by bloodsucking tsetse flies. There is no vaccine and an urgent need for new drugs to combat the disease, as reports of drug resistance are increasing. Several trypanosome species cause AAT and the host range includes both wild and domestic animals, presenting a complex epidemiology. Among these trypanosomes, some have a wide host range including cattle, small ruminants and pigs, while others are restricted to pigs. This host specificity has evolved in two lineages of livestock trypanosomes: Trypanosoma (Nannomonas) simiae and relatives, and T. (Pycnomonas) suis. The evidence is derived from field observations and attempts to experimentally infect different hosts, but the underlying reasons for host specificity are unknown. Our hypothesis is that host specificity has a genetic basis that we can uncover by comparative genomic analysis of pig-specific trypanosomes and their relatives with a broad host range. At Bristol, we have assembled a unique collection of trypanosome isolates that will enable us to address this fundamental question about host specificity, as well as to further understanding of genome content and organisation in these trypanosomes. We will obtain high quality genome sequences from these isolates, complementing the genome data already available from other livestock trypanosomes, and identify sets of genes that are associated with the emergence of host specificity. Not only will this allow us to test hypotheses on how host specificity evolved, but also make predictions about the probability of host switches in the future. The new trypanosome genome sequences we will obtain will also serve as an essential resource for future work on these important parasites, including drug development.

Who might benefit and how?
The beneficiaries of the research in the long term are livestock farmers in Africa, who will gain improved diagnostics and new therapeutics for animal trypanosomiasis, as well as those involved in control of the disease, such as veterinary practitioners and personnel of government departments and non-governmental organisations involved in control of livestock diseases. To reach this audience, we will report our work in both academic and non-academic publications, and on specialist animal health websites. The World Organization for Animal Health (OIE; http://www.oie.int/) acts as a central authority and source of information on animal diseases worldwide. The annual ISCTRC (International Scientific Council for Trypanosomiasis Research and Control) meeting held in sub-Saharan Africa is an important forum to reach those engaged in research and control of animal trypanosomiasis in the endemic regions.

We will engage with the general public and school children about research in parasitology and infectious diseases via events co-ordinated by the Public Engagement Team (PET) at University of Bristol, such as the annual Festival of Nature and Bristol Bright Night. PET organizes science discovery displays at these events and we will develop displays and activities relevant to this project. Participants will gain increased awareness and understanding of animal trypanosomiasis and parasitology in general, and find out about ways to avoid or control the disease.