How does the deadly amoeba, Entamoeba histolytica bind to our cells?

Entamoeba histolytica is the second most deadly eukaryotic parasite to affect humans. It causes amoebiasis, a disease in which the parasite induces dysentery and diarrhoea. If untreated, the infection can then develop into tissue damage, with the amoeba inducing abscesses in tissues such as the liver. These are caused when it ‘bites’ bits off our cells, through a process known as trogocytosis.

One protein complex lies at the centre of this pathology. A heterodimeric lectin is found on the surface of

the amoeba, which binds to carbohydrate-containing molecules on the surfaces of our cells. These interactions are required for the amoeba to attack our tissues and vaccination with parts of the lectin can prevent tissue damage. But we did not know what the lectin looks like or how it recognises carbohydrates.

In this study, Sam Gerard learned to grow Entamoeba histolytica and purified the lectin directly from these cells. He then used cryogenic electron microscopy to see what the lectin looks like and to identify the carbohydrate binding site. The lectin is formed from an ordered core, which consists of a ‘light chain’ and part of a ‘heavy chain’. He showed that the light chain binds to carbohydrates and could characterise the binding site.

Sam also found that the lectin contains an extended lever arm, which can adopt multiple positions relative to the ordered core. Unexpectedly, an antibody which blocks the lectin from binding to cells binds to this lever arm, some distance from the carbohydrate binding site. Future studies will need to resolve this mystery, showing us what the lever arm does and how antibodies against it prevent killing of our cells.

In the meantime, this first view of the lectin shows us how this deadly amoeba recognises our cells and will guide vaccine development as we try to stop the deadly consequences of infection.

Gerard, S.F., Redfield, C. and Higgins, M.K. (2024) Structural basis for carbohydrate recognition by the Gal/GalNAc lectin of Entamoeba histolytica. BioRXIV https://doi.org/10.1101/2024.08.28.610168