Manipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress

ABSTRACT 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 partia...

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Autores principales:	Paul-Christian Burda, Reto Caldelari, Volker T. Heussler
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7b0e0df5fff54219b923e0f97e6701b9
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spelling	oai:doaj.org-article:7b0e0df5fff54219b923e0f97e6701b92021-11-15T15:51:00ZManipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress10.1128/mBio.00139-172150-7511https://doaj.org/article/7b0e0df5fff54219b923e0f97e6701b92017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00139-17https://doaj.org/toc/2150-7511ABSTRACT 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.Paul-Christian BurdaReto CaldelariVolker T. HeusslerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Paul-Christian Burda Reto Caldelari Volker T. Heussler Manipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress
description	ABSTRACT 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.
format	article
author	Paul-Christian Burda Reto Caldelari Volker T. Heussler
author_facet	Paul-Christian Burda Reto Caldelari Volker T. Heussler
author_sort	Paul-Christian Burda
title	Manipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress
title_short	Manipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress
title_full	Manipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress
title_fullStr	Manipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress
title_full_unstemmed	Manipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress
title_sort	manipulation of the host cell membrane during <italic toggle="yes">plasmodium</italic> liver stage egress
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/7b0e0df5fff54219b923e0f97e6701b9
work_keys_str_mv	AT paulchristianburda manipulationofthehostcellmembraneduringitalictoggleyesplasmodiumitalicliverstageegress AT retocaldelari manipulationofthehostcellmembraneduringitalictoggleyesplasmodiumitalicliverstageegress AT volkertheussler manipulationofthehostcellmembraneduringitalictoggleyesplasmodiumitalicliverstageegress
_version_	1718427407360196608

Manipulation of the Host Cell Membrane during <italic toggle="yes">Plasmodium</italic> Liver Stage Egress

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