A Plasmodium phospholipase is involved in disruption of the liver stage parasitophorous vacuole membrane

Burda, Paul-Christian; Rölli, Matthias; Schaffner, Marco; Khan, Shahid M; Janse, Chris J; Heussler, Volker (2015). A Plasmodium phospholipase is involved in disruption of the liver stage parasitophorous vacuole membrane. PLoS pathogens, 11(3), e1004760. Public Library of Science 10.1371/journal.ppat.1004760

Preview

Text Burda_2015.1004760.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (7MB) | Preview

The coordinated exit of intracellular pathogens from host cells is a process critical to the success and spread of an infection. While phospholipases have been shown to play important roles in bacteria host cell egress and virulence, their role in the release of intracellular eukaryotic parasites is largely unknown. We examined a malaria parasite protein with phospholipase activity and found it to be involved in hepatocyte egress. In hepatocytes, Plasmodium parasites are surrounded by a parasitophorous vacuole membrane (PVM), which must be disrupted before parasites are released into the blood. However, on a molecular basis, little is known about how the PVM is ruptured. We show that Plasmodium berghei phospholipase, PbPL, localizes to the PVM in infected hepatocytes. We provide evidence that parasites lacking PbPL undergo completely normal liver stage development until merozoites are produced but have a defect in egress from host hepatocytes. To investigate this further, we established a live-cell imaging-based assay, which enabled us to study the temporal dynamics of PVM rupture on a quantitative basis. Using this assay we could show that PbPL-deficient parasites exhibit impaired PVM rupture, resulting in delayed parasite egress. A wild-type phenotype could be re-established by gene complementation, demonstrating the specificity of the PbPL deletion phenotype. In conclusion, we have identified for the first time a Plasmodium phospholipase that is important for PVM rupture and in turn for parasite exit from the infected hepatocyte and therefore established a key role of a parasite phospholipase in egress.

Interest & Impact

Downloads

194 since deposited on 20 Aug 2015
27 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item