P4 - Mechanical strategies to avoid interspecies competition in trypanosomes

African trypanosomes are probably one of the most extensively studied eukaryotic cells. For more than 120 years they have attracted scientists from very different disciplines. A plethora of trypanosome species parasitize basically all vertebrates, from fish to birds. Their fascinating biology has been detailed by many generations of evolution biologists, geneticists, cell and molecular biologists and, of course, parasitologists. Trypanosomes cause deadly diseases such as human sleeping sickness and nagana in cattle. Today, sleeping sickness is a prototypic neglected tropical disease of poverty, but the beginning of the last century has seen enormous outbreaks and trypanosomes were considered the scourge of Africa. In the past 50 years, Trypanosoma brucei has made a career as cell biological model. Many fundamental discoveries, such as GPI-anchoring of proteins or RNA-editing have been made in trypanosomes, probably because the parasites have evolved streamlined survival strategies using these processes.

Why do the parasites invest so much in membrane recycling. The possible answer suggests a direct link between the cell design of the trypanosome (bauplan), the directional motility of the parasite and the rapid recycling of its cell surface: As obligate extracellular parasites, trypanosomes are under constant surveillance by the host immune system. The parasites are covered with a dense coat of variant surface glycoproteins (VSGs) that shields the plasma membrane and embedded invariant proteins from host antibodies. Trypanosomes have hundreds of VSG types, all of which have a similar structure but are antigenically very different. The parasites stochastically change the VSG type, i.e. they evade the immune response by changing their cell surface coat. This process of antigenic variation essentially continues until the host's defences break down, and death occurs after several weeks to months of infection. In an early stage of antibody response, the parasites use another strategy of immune evasion, namely antibody clearance. The incessant directional motility of the parasites creates a hydrodynamic flow on their cell surface. When antibodies bind to VSGs, the flow force drags the VSG-antibody complexes against the swimming direction towards the posterior pole of the cell. This is where the flagellar pocket is located and the rapid endocytosis rate ensures that the antibody-complexed VSGs are immediately endocytosed. While the antibody is destroyed in the lysosome of the pathogen, the VSG is recycled to the cell surface. Thus, in trypanosomes, motility and the resulting hydrodynamic drag force, are directly involved in the survival and persistence of the parasite. Thus, trypanosome antibody clearance can be considered a prime example of the importance of physics in parasitism.