Biology subjects

Minshall, N.

Publications and source records attributed to Minshall, N..

3 recordsLinked to original sources

bioRxiv2026

An African trypanosome surface protein inhibits amplification of the complement system

African trypanosomes replicate within the blood and tissue spaces of their mammalian hosts. As extracellular pathogens, they are constantly exposed to immune cells and molecules and are susceptible to killing by components of the complement system. In this study, we conducted a large-scale screen of a panel of human complement components against a set of putative T. brucei surface proteins and discovered a novel T. brucei receptor that binds to complement Factor B. Biochemical and structural characterisation of this protein revealed it to be a potent inhibitor of the C3bBb convertase, a central enzyme in amplification of the complement cascade. Structural studies show that this C3bBb receptor bridges C3b and Bb in a conformation which is incompatible with its catalytic activity, directly blocking C3bBb convertase function. This reveals a novel mechanism of C3bBb convertase regulation and deepens insight into how the African trypanosome cell surface has evolved to evade complement-mediated killing.

immunology↗

bioRxiv2026

A Trypanosoma brucei gambiense gene variant confers human serum resistance

Most species of African trypanosomes cannot infect humans due to the presence in our blood of trypanolytic factors (TLFs). These lipoprotein particles contain the apolipoprotein L1 (ApoLI) toxin which, when internalised by trypanosomes, forms pores and causes cell death. However, two subspecies of Trypanosoma brucei have evolved resistance to TLFs and cause Human African Trypanosomiasis (HAT). The mechanism of resistance of T. b. rhodesiense requires a single additional molecule, the serum resistance associated protein SRA. However, the mechanism of resistance of T. b. gambiense, which causes HAT in West Africa, has not been fully understood. Here we identify a single polymorphic variant of a PLAC8-domain containing protein which is required for human serum resistance and call this T. b. gambiense-specific resistance variant, TgsRV. African trypanosomes are coated with a dense layer of many copies of one member of the variant surface glycoprotein protein family (VSGs). For cells expressing some VSGs, TgsRV is sufficient for human serum resistance, while cells which express other VSGs require a second protein, TgsGP in addition to TgsRV. We therefore complete the identification of the molecular players required for human serum resistance by the African trypanosomes.

microbiology↗

bioRxiv2025

Cell surface localisation of GPI-anchored receptors in Trypanosoma brucei

Trypanosoma brucei, the causal agent of Human and Animal African trypanosomiasis proliferates in the extracellular milieu of mammals. It acquires host macromolecular nutrients, by receptor mediated endocytosis. The best characterised cell surface receptor is for transferrin (TfR) and it has been reported to be preferentially localised in the flagellar pocket domain of the plasma membrane, the sole site of endocytosis. In this location the TfR may be inaccessible to adaptive immune system effectors. The T. brucei genome encodes [~]15 TfR variants, and here we compared two, the first attached to the plasma membrane by a single glycosylphosphatidylinositol (GPI)-anchor and the other by two. Transferrin uptake kinetics were similar and rapid for both. Unexpectedly, initial binding of transferrin occurred over the whole cell surface suggesting the TfR was not localised solely in the flagellar pocket. This localisation was confirmed by immunofluorescence assays and was independent of the number of GPI-anchors. Two other GPI-anchored receptors were investigated to determine whether localisation to the whole cell surface was a general property of GPI-anchored receptors. Haptoglobin-haemoglobin uptake assays and immunofluorescence localisation of complement factor H receptor showed both were also whole cell surface localised. The mechanisms by which trypanosome receptors are protected from antibody-mediated attack are more complex than hiding in a pocket.

microbiology↗