Manipulation of the Host Cell Membrane during Plasmodium Liver Stage Egress.

Burda, Paul-Christian; Caldelari, Reto; Heussler, Volker (2017). Manipulation of the Host Cell Membrane during Plasmodium Liver Stage Egress. mBio, 8(2) American Society for Microbiology 10.1128/mBio.00139-17

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A crucial step in the life cycle of Plasmodium parasites is the transition from the liver stage to the blood stage. Hepatocyte-derived merozoites reach the blood vessels of the liver inside host cell-derived vesicles called merosomes. The molecular basis of merosome formation is only partially understood. Here we show that Plasmodium berghei liver stage merozoites, upon rupture of the parasitophorous vacuole membrane, destabilize the host cell membrane (HCM) and induce separation of the host cell actin cytoskeleton from the HCM. At the same time, the phospholipid and protein composition of the HCM appears to be substantially altered. This includes the loss of a phosphatidylinositol 4,5-bisphosphate (PIP2) reporter and the PIP2-dependent actin-plasma membrane linker ezrin from the HCM. Furthermore, transmembrane domain-containing proteins and palmitoylated and myristoylated proteins, as well as glycosylphosphatidylinositol-anchored proteins, lose their HCM localization. Collectively, these findings provide an explanation of HCM destabilization during Plasmodium liver stage egress and thereby contribute to our understanding of the molecular mechanisms that lead to merosome formation.IMPORTANCE Egress from host cells is an essential process for intracellular pathogens, allowing successful infection of other cells and thereby spreading the infection. Here we describe the molecular details of a novel egress strategy of Plasmodium parasites infecting hepatocytes. We show that toward the end of the liver stage, parasites induce a breakdown of the host cell actin cytoskeleton, leading to destabilization of the host cell plasma membrane. This, in turn, results in the formation of membrane vesicles (merosomes), in which parasites can safely migrate from liver tissue to the bloodstream to infect red blood cells and start the pathogenic phase of malaria.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria
08 Faculty of Science > Department of Biology > Institute of Cell Biology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Burda, Paul-Christian; Caldelari, Reto and Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

2150-7511

Publisher:

American Society for Microbiology

Funders:

[4] Swiss National Science Foundation
[81] Evimalar

Language:

English

Submitter:

Volker Heussler

Date Deposited:

10 Aug 2017 09:04

Last Modified:

10 Aug 2017 09:04

Publisher DOI:

10.1128/mBio.00139-17

PubMed ID:

28400525

BORIS DOI:

10.7892/boris.99652

URI:

https://boris.unibe.ch/id/eprint/99652

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