Role of Plasmodium berghei cGMP-dependent protein kinase in late liver stage development

Adebola Falae, Audrey Combe, Anburaj Amaladoss, Teresa G Carvalho, Robert Menard, Purnima Bhanot

Research output: Contribution to journalArticleResearchpeer-review

73 Citations (Scopus)

Abstract

The liver is the first organ infected by Plasmodium sporozoites during malaria infection. In the infected hepatocytes, sporozoites undergo a complex developmental program to eventually generate hepatic merozoites that are released into the bloodstream in membrane-bound vesicles termed merosomes. Parasites blocked at an early developmental stage inside hepatocytes elicit a protective host immune response, making them attractive targets in the effort to develop a pre-erythrocytic stage vaccine. Here, we generated parasites blocked at a late developmental stage inside hepatocytes by conditionally disrupting the Plasmodium berghei cGMP-dependent protein kinase in sporozoites. Mutant sporozoites are able to invade hepatocytes and undergo intracellular development. However, they remain blocked as late liver stages that do not release merosomes into the medium. These late arrested liver stages induce protection in immunized animals. This suggests that, similar to the well studied early liver stages, late stage liver stages too can confer protection from sporozoite challenge.
Original languageEnglish
Pages (from-to)3282 - 3288
Number of pages7
JournalThe Journal of Biological Chemistry
Volume285
Issue number5
DOIs
Publication statusPublished - 2010
Externally publishedYes

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