koningward-plasmodiumtranslocon-2020.pdf (2.09 MB)
Plasmodium translocon component EXP2 facilitates hepatocyte invasion
journal contribution
posted on 2020-11-06, 00:00 authored by J Mello-Vieira, F J Enguita, Tania De Koning-WardTania De Koning-Ward, V Zuzarte-Luís, M M MotaPlasmodium parasites possess a translocon that exports parasite proteins into the infected erythrocyte. Although the translocon components are also expressed during the mosquito and liver stage of infection, their function remains unexplored. Here, using a combination of genetic and chemical assays, we show that the translocon component Exported Protein 2 (EXP2) is critical for invasion of hepatocytes. EXP2 is a pore-forming protein that is secreted from the sporozoite upon contact with the host cell milieu. EXP2-deficient sporozoites are impaired in invasion, which can be rescued by the exogenous administration of recombinant EXP2 and alpha-hemolysin (an S. aureus pore-forming protein), as well as by acid sphingomyelinase. The latter, together with the negative impact of chemical and genetic inhibition of acid sphingomyelinase on invasion, reveals that EXP2 pore-forming activity induces hepatocyte membrane repair, which plays a key role in parasite invasion. Overall, our findings establish a novel and critical function for EXP2 that leads to an active participation of the host cell in Plasmodium sporozoite invasion, challenging the current view of the establishment of liver stage infection.
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Journal
Nature CommunicationsVolume
11Issue
1Article number
5654Pagination
1 - 13Publisher
Nature ResearchLocation
Berlin, GermanyPublisher DOI
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ISSN
2041-1723eISSN
2041-1723Language
EnglishPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2020, The Author(s)Usage metrics
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