Black-necked spitting cobra (Naja nigricollis) phospholipases A2 may cause Trypanosoma brucei death by blocking endocytosis through the flagellar pocket
Authors
Martos-Esteban, Andrea
Macleod, Olivia JS
Maudlin, Isabella
Kalogeropoulos, Konstantinos
Jürgensen, Jonas A
Carrington, Mark
Laustsen, Andreas H
Publication Date
2022-12Journal Title
Scientific Reports
Publisher
Springer Science and Business Media LLC
Volume
12
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Martos-Esteban, A., Macleod, O. J., Maudlin, I., Kalogeropoulos, K., Jürgensen, J. A., Carrington, M., & Laustsen, A. H. (2022). Black-necked spitting cobra (Naja nigricollis) phospholipases A2 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
<jats:title>Abstract</jats:title><jats:p>African trypanosomes, such as <jats:italic>Trypanosoma brucei,</jats:italic> 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<jats:sub>2</jats:sub>. Here, we investigated the effect of <jats:italic>Naja nigricollis</jats:italic> venom on <jats:italic>T. brucei</jats:italic> with the aim of describing the response of the trypanosome to hydrolytic attack on the VSG. We found no evidence for VSG hydrolysis, however, <jats:italic>N. nigricollis</jats:italic> 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<jats:sub>2</jats:sub> present in <jats:italic>N. nigricollis</jats:italic> venom, may be necessary and sufficient for the effects. This study provides new molecular insight into <jats:italic>T. brucei</jats:italic> biology and possibly describes mechanisms that could be exploited for <jats:italic>T. brucei</jats:italic> targeting.</jats:p>
Keywords
Article, /631/61, /631/326, /631/337, /692/699, article
Sponsorship
Wellcome (217138/Z/19/Z)
Identifiers
s41598-022-10091-5, 10091
External DOI: https://doi.org/10.1038/s41598-022-10091-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336152
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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