The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes
Sebastian Zoll and his team at IOCB Prague in collaboration with the group of Mark C. Field from the University of Dundee, UK studied invariant surface glycoprotein ISG75, an abundant type-I transmembrane protein populating the surface of human-infective trypanosomes, that is interesting in the context of treatment of sleeping sickness.
Surface proteins of parasitic protozoa mediate functions essential to survival within a host, including nutrient uptake, environmental sensing, and immune evasion. Several such receptors have been described in African trypanosomes. Together with antigenic variation, they contribute towards persistence within the blood streams of their vertebrate hosts. Among them is a superfamily of invariant surface glycoproteins (ISGs), one of which, ISG75, has been implicated in uptake of the century-old drug suramin still used in treatment of the first stage of acute human sleeping sickness.
By CRISPR/Cas9 knockout and biophysical analysis, researchers provided the first direct evidence that ISG75 indeed binds suramin and mediates uptake of additional naphthol-related compounds, and thus enables entry of at least one structural class of trypanocidal compounds. However, they also observed that ISG75 null cells present only modest attenuation of suramin sensitivity showing that there are additional pathways for suramin accumulation present. This points to a more complex mechanism of suramin acquisition and potential for resistance formation.
The study was published in Microbial Cell.
Read the paper: Alexandr Makarov, Jakub Began, Ileana Corvo Mautone, Erika Pinto, Liam Ferguson, Martin Zoltner, Sebastian Zoll and Mark C. Field (2023). The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes. Microbial Cell 10(2): 18-35. https://doi.org/10.15698/mic2023.02.790
