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Generating Genetically Modified Plasmodium berghei Sporozoites
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Plasmodium translocon component EXP2 facilitates hepatocyte invasion
João Mello-Vieira1, Francisco J Enguita1, Tania F de Koning-Ward2
1Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal.
Nature Communications
|November 7, 2020
Summary
The Plasmodium parasite
Area of Science:
- Parasitology
- Cell Biology
- Infectious Diseases
Background:
- Plasmodium parasites utilize a translocon for protein export into infected erythrocytes.
- The function of translocon components during mosquito and liver stages remains largely unknown.
Purpose of the Study:
- To investigate the role of the translocon component Exported Protein 2 (EXP2) in Plasmodium sporozoite invasion of hepatocytes.
- To elucidate the mechanism by which EXP2 facilitates hepatocyte invasion.
Main Methods:
- Genetic assays to create EXP2-deficient sporozoites.
- Chemical assays involving recombinant EXP2, alpha-hemolysin, and acid sphingomyelinase.
- Inhibition studies of acid sphingomyelinase activity.
Main Results:
- EXP2-deficient sporozoites exhibit impaired hepatocyte invasion.
- Exogenous EXP2, alpha-hemolysin, and acid sphingomyelinase rescue invasion.
- EXP2 pore formation induces hepatocyte membrane repair, crucial for invasion.
Conclusions:
- EXP2 is essential for Plasmodium sporozoite invasion of hepatocytes.
- EXP2's pore-forming activity promotes host cell membrane repair, aiding invasion.
- This highlights a novel mechanism involving host cell participation in liver-stage infection establishment.
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