EastBio: Keeping up with the Joneses: how do trypanosome parasites adapt to coinfection with other trypanosomes?

African trypanosomes are responsible for human disease but their major impact is on livestock in sub Saharan Africa. Here, they cause the disease ‘nagana’, a fatal wasting of cattle responsible for economic losses of around $4B annually in afflicted regions. In the course of infection in animals, trypanosomes moderate their parasitaemia by 'quorum sensing' to generate replication arrested ‘stumpy forms’, which prevent rapid host death and are pre-adapted for transmission by tsetse flies, the disease vector. This generates a chronic infection. However, in the field, trypanosome infections are often comprised of more than strain or species of the parasite as different parasite lines circulate among livestock herds and in game animals in the same geographical region.

In experimental infections our laboratory has demonstrated that over the course of several weeks of coinfection between trypanosome species in rodents, the parasites become adapted to reduce their production of stumpy forms. This helps to them to compete in terms of parasite numbers with the coinfecting strain in the mammalian host but potentially reduces their capacity for effective transmission by tsetse flies.

We have isolated a number of selected parasite lines from coinfections and plan to understand how they have adapted after competition in a coinfection, thereby becoming more virulent. This will involve molecular comparisons of genome sequence, gene expression, chromatin accessibility and protein expression between parasites that have, or have not, been propagated in the presence of competing trypanosome species.

Further we will investigate their relative transmissibility by assaying their ability to infect tsetse flies and establish infections in that disease vector either when alone or as part of a coinfection. This will allow us to understand the consequences of trypanosome coinfection in a mammalian host and upon transmission with relevance for how these parasites interact in the field and the resulting impact on disease severity and spread.