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

Abstract:

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Burda PC,Roelli MA,Schaffner M,Khan SM,Janse CJ,Heussler VT

doi

10.1371/journal.ppat.1004760

subject

Has Abstract

pub_date

2015-03-18 00:00:00

pages

e1004760

issue

3

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-14-02170

journal_volume

11

pub_type

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