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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
08 Faculty of Science > Department of Biology > Institute of Cell Biology
08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Burda, Paul-Christian; Rölli, Matthias and Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
500 Science

ISSN:

1553-7366

Publisher:

Public Library of Science

Language:

English

Submitter:

Volker Heussler

Date Deposited:

20 Aug 2015 10:29

Last Modified:

20 Aug 2015 10:29

Publisher DOI:

10.1371/journal.ppat.1004760

PubMed ID:

25786000

BORIS DOI:

10.7892/boris.71016

URI:

https://boris.unibe.ch/id/eprint/71016

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