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.
Highlights
The controlled exit of intracellular pathogens from host cells is an important step in infection and pathogenesis
Plasmodium parasites infect hepatocytes and red blood cells, and inside these cells they are contained within a vacuole like many other intracellular pathogens
A Plasmodium Phospholipase Is Involved in PVM Rupture surrounding parasitophorous vacuole membrane (PVM) needs to be ruptured
Summary
The controlled exit of intracellular pathogens from host cells is an important step in infection and pathogenesis. This process is important for determining an organism’s life-cycle progression and the efficiency of a secondary infection and the route and timing of egress may influence host immune responses [1]. To escape from host cells, many pathogens have to disrupt two membranes, that of the vacuole they are contained within and the plasma membrane of the host cell. Different molecules have been identified that play a role in the disruption of membranes, the precise mechanisms of membrane degradation are not well understood. Bacterial phospholipases have been identified as playing key roles in the disruption of vacuole membranes (reviewed in [1,2])
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