scholarly journals Manipulation of the Host Cell Membrane during Plasmodium Liver Stage Egress

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Paul-Christian Burda ◽  
Reto Caldelari ◽  
Volker T. Heussler
Keyword(s):  
Plasma Membrane ◽  
Actin Cytoskeleton ◽  
Host Cell ◽  
Membrane Vesicles ◽  
Host Cells ◽  
Cell Plasma Membrane ◽  
Host Cell Membrane ◽  
Liver Stage ◽  
Cell Plasma ◽  
Successful Infection

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. 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.

scholarly journals Invasion by Toxoplasma gondii Establishes a Moving Junction That Selectively Excludes Host Cell Plasma Membrane Proteins on the Basis of Their Membrane Anchoring

1999 ◽  
Vol 190 (12) ◽  
pp. 1783-1792 ◽  
Author(s):  
Dana G. Mordue ◽  
Naishadh Desai ◽  
Michael Dustin ◽  
L. David Sibley
Keyword(s):  
Plasma Membrane ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Transmembrane Domain ◽  
Membrane Lipids ◽  
Transmembrane Proteins ◽  
Host Cells ◽  
Cell Plasma Membrane ◽  
Cell Plasma ◽  
Membrane Anchoring

The protozoan parasite Toxoplasma gondii actively penetrates its host cell by squeezing through a moving junction that forms between the host cell plasma membrane and the parasite. During invasion, this junction selectively controls internalization of host cell plasma membrane components into the parasite-containing vacuole. Membrane lipids flowed past the junction, as shown by the presence of the glycosphingolipid GM1 and the cationic lipid label 1.1′-dihexadecyl-3-3′-3-3′-tetramethylindocarbocyanine (DiIC16). Glycosylphosphatidylinositol (GPI)-anchored surface proteins, such as Sca-1 and CD55, were also readily incorporated into the parasitophorous vacuole (PV). In contrast, host cell transmembrane proteins, including CD44, Na+/K+ ATPase, and β1-integrin, were excluded from the vacuole. To eliminate potential differences in sorting due to the extracellular domains, parasite invasion was examined in host cells transfected with recombinant forms of intercellular adhesion molecule 1 (ICAM-1, CD54) that differed in their mechanism of membrane anchoring. Wild-type ICAM-1, which contains a transmembrane domain, was excluded from the PV, whereas both GPI-anchored ICAM-1 and a mutant of ICAM-1 missing the cytoplasmic tail (ICAM-1–Cyt−) were readily incorporated into the PV membrane. Our results demonstrate that during host cell invasion, Toxoplasma selectively excludes host cell transmembrane proteins at the moving junction by a mechanism that depends on their anchoring in the membrane, thereby creating a nonfusigenic compartment.

scholarly journals ExoS Controls the Cell Contact-Mediated Switch to Effector Secretion in Pseudomonas aeruginosa

2007 ◽  
Vol 190 (8) ◽  
pp. 2726-2738 ◽  
Author(s):  
Michelle Cisz ◽  
Pei-Chung Lee ◽  
Arne Rietsch
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Plasma Membrane ◽  
Host Cell ◽  
Type Iii Secretion ◽  
Host Cells ◽  
Cell Contact ◽  
Cell Plasma Membrane ◽  
Type Iii ◽  
Cell Plasma ◽  
Effector Secretion

ABSTRACT Type III secretion is used by many gram-negative bacterial pathogens to directly deliver protein toxins (effectors) into targeted host cells. In all cases, secretion of effectors is triggered by host cell contact, although the mechanism is unclear. In Pseudomonas aeruginosa, expression of all type III secretion-related genes is up-regulated when secretion is triggered. We were able to visualize this process using a green fluorescent protein reporter system and to use it to monitor the ability of bacteria to trigger effector secretion on cell contact. Surprisingly, the action of one of the major type III secreted effectors, ExoS, prevented triggering of type III secretion by bacteria that subsequently attached to cells, suggesting that triggering of secretion is feedback regulated. Evidence is presented that translocation (secretion of effectors across the host cell plasma membrane) of ExoS is indeed self-regulated and that this inhibition of translocation can be achieved by either of its two enzymatic activities. The translocator proteins PopB, PopD, and PcrV are secreted via the type III secretion system and are required for pore formation and translocation of effectors across the host cell plasma membrane. Here we present data that secretion of translocators is in fact not controlled by calcium, implying that triggering of effector secretion on cell contact represents a switch in secretion specificity, rather than a triggering of secretion per se. The requirement for a host cell cofactor to control effector secretion may help explain the recently observed phenomenon of target cell specificity in both the Yersinia and P. aeruginosa type III secretion systems.

Two Phases Of Ferricyanide Reductase Activity In Ehrlich Cell Plasma Membranes

1992 ◽  
Vol 47 (11-12) ◽  
pp. 929-931 ◽  
Author(s):  
Antonio del Castillo-Olivares ◽  
Javier Márquez ◽  
Ignacio Núñez de Castro ◽  
Miguel Angel Medina
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Reductase Activity ◽  
Membrane Vesicles ◽  
Plasma Membrane Vesicles ◽  
Cell Plasma Membrane ◽  
Ferricyanide Reductase ◽  
Ehrlich Cell ◽  
Cell Plasma ◽  
Two Phases

Ehrlich cell plasma membrane vesicles have a ferricyanide reductase activity that shows two phases. These two phases were kinetically characterized. Evidence is presented for a differential effect of trypsin on both phases

scholarly journals Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus

2015 ◽  
Vol 89 (18) ◽  
pp. 9440-9453 ◽  
Author(s):  
Emmanuel Adu-Gyamfi ◽  
Kristen A. Johnson ◽  
Mark E. Fraser ◽  
Jordan L. Scott ◽  
Smita P. Soni ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Human Cell ◽  
Mammalian Cells ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Cell Plasma Membrane ◽  
Replication Process ◽  
Cell Plasma

ABSTRACTLipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles.IMPORTANCEThe lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry.

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