Black-necked spitting cobra (Naja nigricollis) phospholipases A<sub>2</sub> may cause Trypanosoma brucei death by blocking endocytosis through the flagellar pocket.
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Authors
Martos-Esteban, Andrea
Macleod, Olivia J S
Maudlin, Isabella
Jürgensen, Jonas A
Carrington, Mark
Publication Date
2022-04-16Journal Title
Scientific reports
ISSN
2045-2322
Volume
12
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
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Martos-Esteban, A., Macleod, O. J. S., Maudlin, I., Kalogeropoulos, K., Jürgensen, J. A., Carrington, M., & Laustsen, A. H. (2022). Black-necked spitting cobra (Naja nigricollis) phospholipases A<sub>2</sub> may cause Trypanosoma brucei death by blocking endocytosis through the flagellar pocket.. Scientific reports, 12 (1) https://doi.org/10.1038/s41598-022-10091-5
Abstract
African trypanosomes, such as Trypanosoma brucei, are flagellated protozoa which proliferate in mammals and cause a variety of diseases in people and animals. In a mammalian host, the external face of the African trypanosome plasma membrane is covered by a densely packed coat formed of variant surface glycoprotein (VSG), which counteracts the host's adaptive immune response by antigenic variation. The VSG is attached to the external face of the plasma membrane by covalent attachment of the C-terminus to glycosylphosphatidylinositol. As the trypanosome grows, newly synthesised VSG is added to the plasma membrane by vesicle fusion to the flagellar pocket, the sole location of exo- and endocytosis. Snake venoms contain dozens of components, including proteases and phospholipases A<sub>2</sub>. Here, we investigated the effect of Naja nigricollis venom on T. brucei with the aim of describing the response of the trypanosome to hydrolytic attack on the VSG. We found no evidence for VSG hydrolysis, however, N. nigricollis venom caused: (i) an enlargement of the flagellar pocket, (ii) the Rab11 positive endosomal compartments to adopt an abnormal dispersed localisation, and (iii) cell cycle arrest prior to cytokinesis. Our results indicate that a single protein family, the phospholipases A<sub>2</sub> present in N. nigricollis venom, may be necessary and sufficient for the effects. This study provides new molecular insight into T. brucei biology and possibly describes mechanisms that could be exploited for T. brucei targeting.
Keywords
Animals, Mammals, Humans, Trypanosoma brucei brucei, Variant Surface Glycoproteins, Trypanosoma, Elapid Venoms, Endocytosis, Phospholipases A2, Naja
Sponsorship
Wellcome Trust (217138/Z/19/Z)
Identifiers
35430620, PMC9013370
External DOI: https://doi.org/10.1038/s41598-022-10091-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337296
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