scholarly journals Host Cytoskeleton Remodeling throughout the Blood Stages ofPlasmodium falciparum

2019 ◽  
Vol 83 (4) ◽  
Author(s):  
Jan D. Warncke ◽  
Hans-Peter Beck
Keyword(s):  
Host Cell ◽  
Erythrocyte Membrane ◽  
Membrane Skeleton ◽  
Severe Form ◽  
Content Type ◽  
Host Cell Proteins ◽  
Host Membrane ◽  
Ofplasmodium Falciparum ◽  
Cell Remodeling ◽  
Maurer's Clefts

SUMMARYThe asexual intraerythrocytic development ofPlasmodium falciparum, causing the most severe form of human malaria, is marked by extensive host cell remodeling. Throughout the processes of invasion, intracellular development, and egress, the erythrocyte membrane skeleton is remodeled by the parasite as required for each specific developmental stage. The remodeling is facilitated by a plethora of exported parasite proteins, and the erythrocyte membrane skeleton is the interface of most of the observed interactions between the parasite and host cell proteins. Host cell remodeling has been extensively described and there is a vast body of information on protein export or the description of parasite-induced structures such as Maurer’s clefts or knobs on the host cell surface. Here we specifically review the molecular level of each host cell-remodeling step at each stage of the intraerythrocytic development ofP. falciparum. We describe key events, such as invasion, knob formation, and egress, and identify the interactions between exported parasite proteins and the host cell cytoskeleton. We discuss each remodeling step with respect to time and specific requirement of the developing parasite to explain host cell remodeling in a stage-specific manner. Thus, we highlight the interaction with the host membrane skeleton as a key event in parasite survival.

scholarly journals Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages

2016 ◽  
Vol 113 (17) ◽  
pp. 4800-4805 ◽  
Author(s):  
Megan Dearnley ◽  
Trang Chu ◽  
Yao Zhang ◽  
Oliver Looker ◽  
Changjin Huang ◽  
...  
Keyword(s):  
Erythrocyte Membrane ◽  
Malaria Parasite ◽  
Membrane Skeleton ◽  
Peripheral Circulation ◽  
Coarse Grained ◽  
Mature Stage ◽  
Computationally Efficient ◽  
Vertical Coupling ◽  
Coarse Grained Model ◽  
Cell Remodeling

The sexual blood stage of the human malaria parasitePlasmodium falciparumundergoes remarkable biophysical changes as it prepares for transmission to mosquitoes. During maturation, midstage gametocytes show low deformability and sequester in the bone marrow and spleen cords, thus avoiding clearance during passage through splenic sinuses. Mature gametocytes exhibit increased deformability and reappear in the peripheral circulation, allowing uptake by mosquitoes. Here we define the reversible changes in erythrocyte membrane organization that underpin this biomechanical transformation. Atomic force microscopy reveals that the length of the spectrin cross-members and the size of the skeletal meshwork increase in developing gametocytes, then decrease in mature-stage gametocytes. These changes are accompanied by relocation of actin from the erythrocyte membrane to the Maurer’s clefts. Fluorescence recovery after photobleaching reveals reversible changes in the level of coupling between the membrane skeleton and the plasma membrane. Treatment of midstage gametocytes with cytochalasin D decreases the vertical coupling and increases their filterability. A computationally efficient coarse-grained model of the erythrocyte membrane reveals that restructuring and constraining the spectrin meshwork can fully account for the observed changes in deformability.

scholarly journals Yersinia virulence factors - a sophisticated arsenal for combating host defences

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1370 ◽  
Author(s):  
Steve Atkinson ◽  
Paul Williams
Keyword(s):  
Host Cell ◽  
Yersinia Pseudotuberculosis ◽  
Effector Proteins ◽  
Innate Immune ◽  
Hypodermic Needle ◽  
Human Pathogens ◽  
Host Cell Proteins ◽  
Host Cell Cytoplasm ◽  
Host Membrane ◽  
Cell Suicide

The human pathogensYersinia pseudotuberculosisandYersinia enterocoliticacause enterocolitis, whileYersinia pestisis responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen.

scholarly journals Plasmodium Helical Interspersed Subtelomeric (PHIST) Proteins, at the Center of Host Cell Remodeling

2016 ◽  
Vol 80 (4) ◽  
pp. 905-927 ◽  
Author(s):  
Jan D. Warncke ◽  
Ioannis Vakonakis ◽  
Hans-Peter Beck
Keyword(s):  
Host Cell ◽  
Current Knowledge ◽  
Surface Display ◽  
Protein Family ◽  
Content Type ◽  
Cellular Processes ◽  
Cell Remodeling ◽  
Definition Of ◽  
Few Data ◽  
Available Information

SUMMARYDuring the asexual cycle,Plasmodium falciparumextensively remodels the human erythrocyte to make it a suitable host cell. A large number of exported proteins facilitate this remodeling process, which causes erythrocytes to become more rigid, cytoadherent, and permeable for nutrients and metabolic products. Among the exported proteins, a family of 89 proteins, called thePlasmodiumhelical interspersed subtelomeric (PHIST) protein family, has been identified. While also found in otherPlasmodiumspecies, the PHIST family is greatly expanded inP. falciparum. Although a decade has passed since their first description, to date, most PHIST proteins remain uncharacterized and are of unknown function and localization within the host cell, and there are few data on their interactions with other host or parasite proteins. However, over the past few years, PHIST proteins have been mentioned in the literature at an increasing rate owing to their presence at various localizations within the infected erythrocyte. Expression of PHIST proteins has been implicated in molecular and cellular processes such as the surface display of PfEMP1, gametocytogenesis, changes in cell rigidity, and also cerebral and pregnancy-associated malaria. Thus, we conclude that PHIST proteins are central to host cell remodeling, but despite their obvious importance in pathology, PHIST proteins seem to be understudied. Here we review current knowledge, shed light on the definition of PHIST proteins, and discuss these proteins with respect to their localization and probable function. We take into consideration interaction studies, microarray analyses, or data from blood samples from naturally infected patients to combine all available information on this protein family.

scholarly journals An unusual trafficking domain in MSRP6 defines a complex needed for Maurer’s clefts anchoring and maintenance in P. falciparum infected red blood cells

2021 ◽  
Author(s):  
Alexandra Blancke Soares ◽  
Jan Stäcker ◽  
Svenja Schwald ◽  
Wieteke Hoijmakers ◽  
Nahla Galal Metwally ◽  
...  
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Virulence Factor ◽  
Structural Integrity ◽  
Surface Display ◽  
Parasite Survival ◽  
Cell Remodeling ◽  
Infected Rbcs ◽  
Host Cell Surface ◽  
Maurer's Clefts

AbstractIntracellular malaria blood stage parasites remodel their host cell, a process essential for parasite survival and a cause of pathology in malaria infections. Host cell remodeling depends on the export of different classes of exported parasite proteins into the infected red blood cell (RBC). Here we show that members of a recently discovered group of difficult to predict exported proteins harbor an N-terminal export domain, similar to other classes of exported proteins, indicating that this is a common theme among all classes of exported proteins. For one such protein, MSRP6 (MSP-7 related protein 6), we identified a second, untypical export-mediating domain that corresponded to its MSP7-like region. In addition to its function in export, this domain also mediated attachment to the Maurer’s clefts, prominent parasite-induced structures in the host cell where MSRP6 is located. Using BioID with the Maurer’s clefts attachment domain of MSRP6 to identify interactors and compartment neighbors in live parasites we discovered a novel complex of proteins at the Maurer’s clefts. We show that this complex is necessary for the anchoring and maintaining the structural integrity of the Maurer’s clefts. The Maurer’s clefts are believed to be involved in the transport of the major virulence factor PfEMP1 to the host cell surface where it mediates cytoadherence of infected RBCs to endothelial cells, a main reason for the importance of host cell modifications for parasite virulence in the human host. Taking advantage of MSRP6 complex mutants and IT4 parasites that we modified to express only one specific PfEMP1 we find that abolishing Maurer’s clefts anchoring was neither needed for PfEMP1 transport to the host cell surface nor for cytoadherence. Altogether, this work reveals parasite proteins involved in Maurer’s clefts anchoring and maintenance and unexpectedly finds that these functions are dispensable for virulence factor transport and surface display.

scholarly journals Precision analysis for the determination of steric mass action parameters using eight tobacco host cell proteins

2021 ◽  
pp. 462379
Author(s):  
C.R. Bernau ◽  
R.C. Jäpel ◽  
J.W. Hübbers ◽  
S. Nölting ◽  
P. Opdensteinen ◽  
...  
Keyword(s):  
Host Cell ◽  
Mass Action ◽  
Precision Analysis ◽  
Host Cell Proteins

scholarly journals Trafficking and Association of Plasmodium falciparum MC-2TM with the Maurer’s Clefts

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 431
Author(s):  
Raghavendra Yadavalli ◽  
John W. Peterson ◽  
Judith A. Drazba ◽  
Tobili Y. Sam-Yellowe
Keyword(s):  
Plasmodium Falciparum ◽  
Erythrocyte Membrane ◽  
Sodium Carbonate ◽  
Infected Erythrocyte ◽  
Brefeldin A ◽  
Specific Expression ◽  
Lipid Interactions ◽  
And Topology ◽  
Streptolysin O ◽  
Maurer's Clefts

In this study, we investigated stage specific expression, trafficking, solubility and topology of endogenous PfMC-2TM in P. falciparum (3D7) infected erythrocytes. Following Brefeldin A (BFA) treatment of parasites, PfMC-2TM traffic was evaluated using immunofluorescence with antibodies reactive with PfMC-2TM. PfMC-2TM is sensitive to BFA treatment and permeabilization of infected erythrocytes with streptolysin O (SLO) and saponin, showed that the N and C-termini of PfMC-2TM are exposed to the erythrocyte cytoplasm with the central portion of the protein protected in the MC membranes. PfMC-2TM was expressed as early as 4 h post invasion (hpi), was tightly colocalized with REX-1 and trafficked to the erythrocyte membrane without a change in solubility. PfMC-2TM associated with the MC and infected erythrocyte membrane and was resistant to extraction with alkaline sodium carbonate, suggestive of protein-lipid interactions with membranes of the MC and erythrocyte. PfMC-2TM is an additional marker of the nascent MCs.

Analytics of host cell proteins (HCPs): lessons from biopharmaceutical mAb analysis for Gene therapy products

2021 ◽  
Vol 71 ◽  
pp. 98-104
Author(s):  
Daniel G Bracewell ◽  
Victoria Smith ◽  
Mike Delahaye ◽  
C Mark Smales
Keyword(s):  
Gene Therapy ◽  
Host Cell ◽  
Host Cell Proteins

scholarly journals TolC-Dependent Modulation of Host Cell Death by the Francisella tularensis Live Vaccine Strain

2014 ◽  
Vol 82 (5) ◽  
pp. 2068-2078 ◽  
Author(s):  
Christopher R. Doyle ◽  
Ji-An Pan ◽  
Patricio Mena ◽  
Wei-Xing Zong ◽  
David G. Thanassi
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Host Cell ◽  
Francisella Tularensis ◽  
Vaccine Strain ◽  
Live Vaccine ◽  
Live Vaccine Strain ◽  
Type I ◽  
Content Type ◽  
Host Cell Death

ABSTRACTFrancisella tularensisis a facultative intracellular, Gram-negative pathogen and the causative agent of tularemia. We previously identified TolC as a virulence factor of theF. tularensislive vaccine strain (LVS) and demonstrated that a ΔtolCmutant exhibits increased cytotoxicity toward host cells and elicits increased proinflammatory responses compared to those of the wild-type (WT) strain. TolC is the outer membrane channel component used by the type I secretion pathway to export toxins and other bacterial virulence factors. Here, we show that the LVS delays activation of the intrinsic apoptotic pathway in a TolC-dependent manner, both during infection of primary macrophages and during organ colonization in mice. The TolC-dependent delay in host cell death is required forF. tularensisto preserve its intracellular replicative niche. We demonstrate that TolC-mediated inhibition of apoptosis is an active process and not due to defects in the structural integrity of the ΔtolCmutant. These findings support a model wherein the immunomodulatory capacity ofF. tularensisrelies, at least in part, on TolC-secreted effectors. Finally, mice vaccinated with the ΔtolCLVS are protected from lethal challenge and clear challenge doses faster than WT-vaccinated mice, demonstrating that the altered host responses to primary infection with the ΔtolCmutant led to altered adaptive immune responses. Taken together, our data demonstrate that TolC is required for temporal modulation of host cell death during infection byF. tularensisand highlight how shifts in the magnitude and timing of host innate immune responses may lead to dramatic changes in the outcome of infection.

scholarly journals A Cluster of Ring Stage–specific Genes Linked to a Locus Implicated in Cytoadherence inPlasmodium falciparumCodes for PEXEL-negative and PEXEL-positive Proteins Exported into the Host Cell

2006 ◽  
Vol 17 (8) ◽  
pp. 3613-3624 ◽  
Author(s):  
Tobias Spielmann ◽  
Paula L. Hawthorne ◽  
Matthew W.A. Dixon ◽  
Mandy Hannemann ◽  
Kathleen Klotz ◽  
...  
Keyword(s):  
Host Cell ◽  
Major Part ◽  
Asexual Development ◽  
Sequence Motif ◽  
Ring Stage ◽  
Systematic Analysis ◽  
Development Cycle ◽  
Cell Remodeling ◽  
Membrane Compartments ◽  
Exported Protein

Blood stages of Plasmodium falciparum export proteins into their erythrocyte host, thereby inducing extensive host cell modifications that become apparent after the first half of the asexual development cycle (ring stage). This is responsible for a major part of parasite virulence. Export of many parasite proteins depends on a sequence motif termed Plasmodium export element (PEXEL) or vacuolar transport signal (VTS). This motif has allowed the prediction of the Plasmodium exportome. Using published genome sequence, we redetermined the boundaries of a previously studied region linked to P. falciparum virulence, reducing the number of candidate genes in this region to 13. Among these, we identified a cluster of four ring stage-specific genes, one of which is known to encode an exported protein. We demonstrate that all four genes code for proteins exported into the host cell, although only two genes contain an obvious PEXEL/VTS motif. We propose that the systematic analysis of ring stage-specific genes will reveal a cohort of exported proteins not present in the currently predicted exportome. Moreover, this provides further evidence that host cell remodeling is a major task of this developmental stage. Biochemical and photobleaching studies using these proteins reveal new properties of the parasite-induced membrane compartments in the host cell. This has important implications for the biogenesis and connectivity of these structures.

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