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Black-necked spitting cobra (Naja nigricollis) phospholipases A2 may cause Trypanosoma brucei death by blocking endocytosis through the flagellar pocket.

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cam.issuedOnline2022-04-16
dc.contributor.authorMartos-Esteban, Andrea
dc.contributor.authorMacleod, Olivia JS
dc.contributor.authorMaudlin, Isabella
dc.contributor.authorKalogeropoulos, Konstantinos
dc.contributor.authorJürgensen, Jonas A
dc.contributor.authorCarrington, Mark
dc.contributor.authorLaustsen, Andreas H
dc.contributor.orcidKalogeropoulos, Konstantinos [0000-0003-3907-9281]
dc.contributor.orcidLaustsen, Andreas H [0000-0001-6918-5574]
dc.date.accessioned2022-05-19T01:03:12Z
dc.date.available2022-05-19T01:03:12Z
dc.date.issued2022-04-16
dc.date.updated2022-05-19T01:03:12Z
dc.description.abstractAfrican 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 A2. 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 A2 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.
dc.identifier.doi10.17863/CAM.84711
dc.identifier.eissn2045-2322
dc.identifier.issn2045-2322
dc.identifier.other35430620
dc.identifier.otherPMC9013370
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337296
dc.languageeng
dc.language.isoeng
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101563288
dc.sourceessn: 2045-2322
dc.subjectAnimals
dc.subjectElapid Venoms
dc.subjectEndocytosis
dc.subjectHumans
dc.subjectMammals
dc.subjectNaja
dc.subjectPhospholipases A2
dc.subjectTrypanosoma brucei brucei
dc.subjectVariant Surface Glycoproteins, Trypanosoma
dc.titleBlack-necked spitting cobra (Naja nigricollis) phospholipases A2 may cause Trypanosoma brucei death by blocking endocytosis through the flagellar pocket.
dc.typeArticle
dcterms.dateAccepted2022-03-25
prism.issueIdentifier1
prism.publicationNameSci Rep
prism.volume12
pubs.funder-project-idWellcome Trust (217138/Z/19/Z)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41598-022-10091-5

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