Hold tight: Trans-sialidase allows Trypanosoma congolense to attach to host cells

Abstract text

Nagana, an animal disease caused by African trypanosomes, affects both wild and domestic animals. Cattle are especially susceptible and cause the economic loss of roughly 1 billion US dollars annually, crippling developing countries in sub-Saharan Africa. Among the several trypanosome species which cause nagana, Trypanosoma (T.) congolense is the most pathogenic. A key feature involved in T. congolense infection in both the mammalian host and the insect vector, the tsetse fly, is its ability to attach to host cells such as red blood cells (RBCs), blood vessel walls, and the fly proboscis. This attachment can harm host cells and is done in a sialic acid dependent manner. While the mechanism of this attachment has been hypothesized to be proteins of the trans-sialidase family, this has never been proven. Here, we aimed to better characterize this attachment and its mechanism in T. congolense. We first performed binding assays by adding RBCs from different host species to T. congolense culture. We found that T. conoglense preferentially binds to host species which have alpha 2-3 linked sialic acid on their RBC surface. We then pre-treated either T. congolense cells or host RBCs with sialidase or with different sialic acid donors and acceptors and checked for binding. These results strongly point to trans-sialidase being the cause of binding. We then verified these results in vitro by immobilizing recombinant trans-sialidase (TconTS) and repeating binding experiments with RBCs from different host species as well as pre-treatment with sialic acid donor or acceptor substrates. Finally, we aimed to introduce TconTS into a sister species of trypanosome, Trypanosoma brucei, which does not attach to host cells, to show that TconTS is truly the cause of binding. Taken together, these results show that T. conoglense preferentially binds to certain host species, that trans-sialidase is the cause of parasite binding to host tissues, and, as binding is crucial to parasite survival in both the mammalian host and insect vector, is a potential target against AAT.