Within the liver a single Plasmodium parasite transforms into tens of thousands of blood infective forms to cause malaria. Through an integrative approach that combined gene sequencing technologies and a forward genetic screen in Iiver cells, we discovered several human genes that are critical to Plasmodium parasite development. We found that host aquaporin 3 (AQP3), a water and glycerol channel, is highly expressed in Plasmodium infected hepatocytes compared to uninfected cells. This aquaglyceroporin localizes to the parasitophorous vacuole, the compartmental interface between the host and pathogen with a temporal pattern that correlates with the parasite’s expansion in the liver. Depletion or elimination of host AQP3 expression significantly reduces P. berghei parasite burden during the liver stage and chemical disruption by AQP3 inhibitors reduces P. falciparum asexual blood stage and P. berghei liver stage parasite load. Thus we revealed a potential route for host-dependent nutrient acquisition by Plasmodium by mapping the transcriptional changes that occur in hepatocytes throughout P. berghei infection. This study highlights Plasmodium’s dependence on host factors within hepatocytes, which may be leveraged to develop host-based targets for disease control as well as understand the biology of the Plasmodium parasite.

Chemical tools for unraveling parasite biology

2019 Fall National Meeting

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