Invariant Surface Glycoproteins of Trypanosoma congolense

African trypanosomes are single-celled, eukaryotic pathogens of humans and animals in sub-Saharan Africa. As they are extracellular parasites, their cell surface forms the primary host-pathogen interface and must balance nutrient uptake and other necessary functions with host immune evasion. Invariant Surface Glycoproteins (ISGs) are a large family of surface proteins with recent expansion and diversification in Trypanosoma congolense. The function of ISGs in T. congolense is unknown, and is the focus of this PhD.

I aim to identify components of mammalian serum that bind selected ISGs, and to characterise these interactions using biochemical and cellular methods. I also intend to determine whether all, or a subset, of the available ISGs are expressed at any given time during the bloodstream life stage, and whether this differs between short- and long-term cultured T. congolense isolates.

Pulldowns were performed using biotinylated HEK293-expressed ISGs bound to streptavidin coated magnetic beads to precipitate any ligand from goat serum. Thus far, one ISG (TcIL3000_5_50) has pulled down C4 binding protein (alpha chain) (C4BP(A)). C4BP negatively regulates the classical and lectin pathways of the mammalian complement system. Pending validation, this result supports a hypothesis that some ISGs may present host C4BP(A) to protect the trypanosome from lysis by complement (a strategy used by many bacterial, viral and fungal pathogens).

Immediate future work will aim to assess whether other ISGs bind the same or different ligands from mammalian sera, which will determine whether this PhD focuses on a single interaction, or aims to characterise the functional diversity of T. congolense ISGs.