Discovery of Druggable Host Factors Critical to Plasmodium Liver-Stage Infection.

Journal Article (Journal Article)

Plasmodium parasites undergo an obligatory and asymptomatic developmental stage within the liver before infecting red blood cells to cause malaria. The hijacked host pathways critical to parasite infection during this hepatic phase remain poorly understood. Here, we implemented a forward genetic screen to identify over 100 host factors within the human druggable genome that are critical to P. berghei infection in hepatoma cells. Notably, we found knockdown of genes involved in protein trafficking pathways to be detrimental to parasite infection. The disruption of protein trafficking modulators, including COPB2 and GGA1, decreases P. berghei parasite size, and an immunofluorescence study suggests that these proteins are recruited to the Plasmodium parasitophorous vacuole in infected hepatocytes. These findings reveal that various host intracellular protein trafficking pathways are subverted by Plasmodium parasites during the liver stage and provide new insights into their manipulation for growth and development.

Full Text

Duke Authors

Cited Authors

  • Raphemot, R; Toro-Moreno, M; Lu, K-Y; Posfai, D; Derbyshire, ER

Published Date

  • September 2019

Published In

Volume / Issue

  • 26 / 9

Start / End Page

  • 1253 - 1262.e5

PubMed ID

  • 31257182

Pubmed Central ID

  • PMC6754275

Electronic International Standard Serial Number (EISSN)

  • 2451-9448

International Standard Serial Number (ISSN)

  • 2451-9456

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2019.05.011


  • eng