scholarly journals Unique Endomembrane Systems and Virulence in Pathogenic Protozoa

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 822
Author(s):  
Mark F. Wiser
Keyword(s):  
Immune System ◽  
Host Cell ◽  
Erythrocyte Membrane ◽  
Malaria Parasite ◽  
Host Cells ◽  
Tissue Invasion ◽  
Intracellular Parasites ◽  
Broad Overview

Virulence in pathogenic protozoa is often tied to secretory processes such as the expression of adhesins on parasite surfaces or the secretion of proteases to assisted in tissue invasion and other proteins to avoid the immune system. This review is a broad overview of the endomembrane systems of pathogenic protozoa with a focus on Giardia, Trichomonas, Entamoeba, kinetoplastids, and apicomplexans. The focus is on unique features of these protozoa and how these features relate to virulence. In general, the basic elements of the endocytic and exocytic pathways are present in all protozoa. Some of these elements, especially the endosomal compartments, have been repurposed by the various species and quite often the repurposing is associated with virulence. The Apicomplexa exhibit the most unique endomembrane systems. This includes unique secretory organelles that play a central role in interactions between parasite and host and are involved in the invasion of host cells. Furthermore, as intracellular parasites, the apicomplexans extensively modify their host cells through the secretion of proteins and other material into the host cell. This includes a unique targeting motif for proteins destined for the host cell. Most notable among the apicomplexans is the malaria parasite, which extensively modifies and exports numerous proteins into the host erythrocyte. These modifications of the host erythrocyte include the formation of unique membranes and structures in the host erythrocyte cytoplasm and on the erythrocyte membrane. The transport of parasite proteins to the host erythrocyte involves several unique mechanisms and components, as well as the generation of compartments within the erythrocyte that participate in extraparasite trafficking.

scholarly journals Pathogen induced subversion of NAD+ metabolism mediating host cell death: a target for development of chemotherapeutics

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ayushi Chaurasiya ◽  
Swati Garg ◽  
Ashish Khanna ◽  
Chintam Narayana ◽  
Ved Prakash Dwivedi ◽  
...  
Keyword(s):  
Cell Death ◽  
Host Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Malaria Parasite ◽  
Host Cells ◽  
Nicotinamide Adenine ◽  
Targeted Therapeutics ◽  
Nad Metabolism ◽  
Host Cell Death ◽  
Nanomolar Range

AbstractHijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD+-glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD+). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD+ levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD+ modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD+-glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD+ homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics.

The cell as an extreme environment

1979 ◽  
Vol 204 (1155) ◽  
pp. 199-210 ◽  
Keyword(s):  
Host Cell ◽  
Extreme Environments ◽  
Extreme Environment ◽  
Host Cells ◽  
Limiting Factors ◽  
Limiting Factor ◽  
Free Access ◽  
Fitness Traits ◽  
Intracellular Parasites ◽  
The Face

Living cells and their intracellular parasites show many of the characteristics ascribed to extreme environments and their dominant species. The diversity of species colonizing intracellular habitats is low, and successful inhabitants exhibit special fitness traits that often render them obligately dependent on residence within a host cell. However, the diversity-limiting factor in the extreme environment of the host cell interior is not abiotic, as it is in conventional extreme environments. It is biotic: the living cell itself and its many activities. Host cells bar the entrance to most would-be parasites, they destroy most of those that do manage to get inside, and they deny parasites free access to many components of their soluble metabolite pools. Successful intracellular parasites have evolved fitness traits that give them the capacity to survive in the face of diversity-limiting factors or to modify the intracellular habitat so that those factors no longer operate. Looking on the cell as an extreme habitat emphasizes its simultaneous roles as environment, antagonist, and competitor.

scholarly journals Molecular cloning and characterization ofNcROP2Fam-1, a member of the ROP2 family of rhoptry proteins inNeospora caninumthat is targeted by antibodies neutralizing host cell invasionin vitro

Parasitology ◽  
2013 ◽  
Vol 140 (8) ◽  
pp. 1033-1050 ◽  
Author(s):  
FERIAL ALAEDDINE ◽  
ANDREW HEMPHILL ◽  
KARIM DEBACHE ◽  
CHRISTOPHE GUIONAUD
Keyword(s):  
Host Cell ◽  
Family Member ◽  
Vaccine Candidate ◽  
Neospora Caninum ◽  
Parasitophorous Vacuole ◽  
Host Cells ◽  
General Belief ◽  
Intracellular Parasites ◽  
Promising Vaccine Candidate

SUMMARYRecent publications demonstrated that a fragment of aNeospora caninumROP2 family member antigen represents a promising vaccine candidate. We here report on the cloning of the cDNA encoding this protein,N. caninumROP2 family member 1 (NcROP2Fam-1), its molecular characterization and localization. The protein possesses the hallmarks of ROP2 family members and is apparently devoid of catalytic activity. NcROP2Fam-1 is synthesized as a pre-pro-protein that is matured to 2 proteins of 49 and 55 kDa that localize to rhoptry bulbs. Upon invasion the protein is associated with the nascent parasitophorous vacuole membrane (PVM), evacuoles surrounding the host cell nucleus and, in some instances, the surface of intracellular parasites. Staining was also observed within the cyst wall of ‘cysts’ producedin vitro. Interestingly, NcROP2Fam-1 was also detected on the surface of extracellular parasites entering the host cells and antibodies directed against NcROP2Fam-1-specific peptides partially neutralized invasionin vitro. We conclude that, in spite of the general belief that ROP2 family proteins are intracellular antigens, NcROP2Fam-1 can also be considered as an extracellular antigen, a property that should be taken into account in further experiments employing ROP2 family proteins as vaccines.

scholarly journals Signal-mediated export of proteins from the malaria parasite to the host erythrocyte

2005 ◽  
Vol 171 (4) ◽  
pp. 587-592 ◽  
Author(s):  
Matthias Marti ◽  
Jake Baum ◽  
Melanie Rug ◽  
Leann Tilley ◽  
Alan F. Cowman
Keyword(s):  
Host Cell ◽  
Malaria Parasite ◽  
Human Erythrocytes ◽  
Virulence Proteins ◽  
Genus Plasmodium ◽  
Intracellular Parasites

Intracellular parasites from the genus Plasmodium reside and multiply in a variety of cells during their development. After invasion of human erythrocytes, asexual stages from the most virulent malaria parasite, P. falciparum, drastically change their host cell and export remodelling and virulence proteins. Recent data demonstrate that a specific NH2-terminal signal conserved across the genus Plasmodium plays a central role in this export process.

Trypanosoma cruzi does not induce apoptosis in murine fibroblasts

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 167-175 ◽  
Author(s):  
R. K. CLARK ◽  
R. E. KUHN
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Cell Apoptosis ◽  
Membrane Integrity ◽  
Host Cells ◽  
Mammalian Host ◽  
Host Cell Apoptosis ◽  
Intracellular Parasites ◽  
Murine Fibroblasts ◽  
Infected Cells

The intracellular cycle of Trypanosoma cruzi in mammalian host cells involves the differentiation of dividing amastigote forms into flagellated trypomastigote forms. The mechanism(s) regulating the growth and differentiation of the intracellular parasites is (are) not known. The number of parasites in infected cells can be several hundred and may be enough to induce apoptosis, a suicide-like death programme, generating products (e.g. nuclear proteins) that could function as signals to initiate the differentiation of amastigotes into trypomastigotes. Murine fibroblasts infected with T. cruzi were examined during a 5-day course of infection for evidence of apoptosis. However, characteristics of apoptosis, including degeneration of nuclear structure, condensation of chromatin, loss of plasma membrane integrity, or the cleavage of DNA into nucleosomal fragments, were not observed. Therefore, it is unlikely that products resulting from host cell apoptosis function to induce parasite differentiation. The possibility that T. cruzi might inhibit host cell apoptosis by increasing intracellular levels of Bcl-2, an endogenous inhibitor of apoptosis, was then investigated. Analysis of infected cells by flow cytometry did not demonstrate a significant amount of intracellular Bcl-2. This suggests that if the parasite is inhibiting host cell apoptosis, it is by a method that does not involve increasing levels of Bcl-2.

scholarly journals Hide-and-Seek: A Game Played between Parasitic Protists and Their Hosts

2021 ◽  
Vol 9 (12) ◽  
pp. 2434
Author(s):  
Iva Kolářová ◽  
Andrea Valigurová
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Host Cell ◽  
Nutrient Supply ◽  
Host Organism ◽  
Cell Functions ◽  
Tight Contact ◽  
Intracellular Parasites ◽  
Gain Access

After invading the host organism, a battle occurs between the parasitic protists and the host’s immune system, the result of which determines not only whether and how well the host survives and recovers, but also the fate of the parasite itself. The exact weaponry of this battle depends, among others, on the parasite localisation. While some parasitic protists do not invade the host cell at all (extracellular parasites), others have developed successful intracellular lifestyles (intracellular parasites) or attack only the surface of the host cell (epicellular parasites). Epicellular and intracellular protist parasites have developed various mechanisms to hijack host cell functions to escape cellular defences and immune responses, and, finally, to gain access to host nutrients. They use various evasion tactics to secure the tight contact with the host cell and the direct nutrient supply. This review focuses on the adaptations and evasion strategies of parasitic protists on the example of two very successful parasites of medical significance, Cryptosporidium and Leishmania, while discussing different localisation (epicellular vs. intracellular) with respect to the host cell.

scholarly journals Investigation of Bartonella quintana Host Immune Evasion

2021 ◽  
Author(s):  
◽  
Callum Lambert
Keyword(s):  
Immune System ◽  
Actin Cytoskeleton ◽  
Host Cell ◽  
Immune Evasion ◽  
Mammalian Species ◽  
Effector Proteins ◽  
Host Cells ◽  
Sand Fly ◽  
Host Immune System ◽  
Bartonella Quintana

<p>Bartonella is a genus of gram-negative alphaproteobacteria that infect mammals, causing both acute and chronic disease. Bartonella are re-emerging infectious pathogens that cause a variety of clinical syndromes in humans worldwide, including cat scratch disease, trench fever, bacillary angiomatosis, and endocarditis. Bartonella spp. are spread by biting arthropods such as the sand fly, cat flea, and body louse, and have been isolated from almost all mammalian species tested. Bartonella are a re-emerging concern as the number of confirmed Bartonella diagnoses are increasing, primarily in immunocompromised groups, homeless populations, refugee camps, and in veterinary workers. The three primary human disease-causing Bartonella spp. are B. henselae, B. quintana, and B. bacilliformis. Bartonella are known to subvert the host immune system and persist within the host, often causing bacteraemia which is difficult to effectively diagnose and treat. B. quintana infects humans; after introduction to the skin the bacteria implement numerous immune evasion mechanisms to enter the bloodstream and invade erythrocytes. The mechanisms by which B. quintana modulates and evades the immune system during early infection are almost entirely unknown. Following exposure to B. quintana, the bacteria encounter host immune cells but survive, evading these cells and disseminating into the lymphatic system and eventually bloodstream. This thesis project aimed to dissect the interactions between B. quintana and the human innate immune system to better understand the early stages of infection. A gentamicin protection assay was developed to investigate the ability of THP-1 macrophages, representing human macrophages present in the skin, to internalise B. quintana. These data revealed THP-1 cells were unable to effectively internalise B. quintana, although the mechanism responsible was not determined. Subsequent experiments investigated the role of the B. quintana Type IV secreted effector protein BepA1 in the inhibition of internalisation. Bacterial effector proteins often pathogenically modulate host cell signalling to benefit the bacteria, i.e., altering the actin cytoskeleton to inhibit phagocytosis or supressing immune responses. It was hypothesised BepA1 could play a role in inhibiting phagocytosis; therefore, the host cell target of BepA1 was investigated with a yeast two-hybrid system assay. The human protein Myozap was uncovered as a potential protein that interacts with BepA1. Myozap is expressed in cardiac and lung tissue as well as epithelial and endothelial cells, where it modulates Rho-dependent actin signalling, potentially affecting the actin cytoskeleton and the transcription factor MRTF-A, which influences immune reaction through modulation of NF-κB. To investigate the functional effects of BepA1 activity in host cells, HeLa cells were transfected with BepA1; cell migration and cytokine secretion were assessed, revealing a decrease in pro-inflammatory cytokines in BepA1-transfected cells in response to TNF-a stimulation. These data suggest BepA1 may be deployed by B. quintana during infection to suppress the host immune response and avoid clearance from the site of infection. This research addressed a major gap in our understanding of B. quintana infections. Improving our understanding of the interactions between Bartonella and the host immune system is an essential first step in the development of improved diagnostic techniques and treatments.   </p>

scholarly journals From infection to cancer: how DNA tumour viruses alter host cell central carbon and lipid metabolism

Open Biology ◽  
2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Kamini L. Magon ◽  
Joanna L. Parish
Keyword(s):  
Host Cell ◽  
Cell Metabolism ◽  
Life Cycles ◽  
Host Cells ◽  
Barr Virus ◽  
Cell Functions ◽  
Intracellular Parasites ◽  
B Virus ◽  
Central Carbon ◽  
Epstein Barr

Infections cause 13% of all cancers globally, and DNA tumour viruses account for almost 60% of these cancers. All viruses are obligate intracellular parasites and hijack host cell functions to replicate and complete their life cycles to produce progeny virions. While many aspects of viral manipulation of host cells have been studied, how DNA tumour viruses manipulate host cell metabolism and whether metabolic alterations in the virus life cycle contribute to carcinogenesis are not well understood. In this review, we compare the differences in central carbon and fatty acid metabolism in host cells following infection, oncogenic transformation, and virus-driven cancer of DNA tumour viruses including: Epstein–Barr virus, hepatitis B virus, human papillomavirus, Kaposi's sarcoma-associated herpesvirus and Merkel cell polyomavirus.

scholarly journals Lipid rafts and pathogens: the art of deception and exploitation

2019 ◽  
Vol 61 (5) ◽  
pp. 601-610 ◽  
Author(s):  
Michael I. Bukrinsky ◽  
Nigora Mukhamedova ◽  
Dmitri Sviridov
Keyword(s):  
Immune Response ◽  
Plasma Membrane ◽  
Host Cell ◽  
Lipid Rafts ◽  
Therapeutic Approach ◽  
Host Cells ◽  
Infectious Agents ◽  
Systematic Overview ◽  
Intracellular Parasites ◽  
A Cell

Lipid rafts, solid regions of the plasma membrane enriched in cholesterol and glycosphingolipids, are essential parts of a cell. Functionally, lipid rafts present a platform that facilitates interaction of cells with the outside world. However, the unique properties of lipid rafts required to fulfill this function at the same time make them susceptible to exploitation by pathogens. Many steps of pathogen interaction with host cells, and sometimes all steps within the entire lifecycle of various pathogens, rely on host lipid rafts. Such steps as binding of pathogens to the host cells, invasion of intracellular parasites into the cell, the intracellular dwelling of parasites, microbial assembly and exit from the host cell, and microbe transfer from one cell to another all involve lipid rafts. Interaction also includes modification of lipid rafts in host cells, inflicted by pathogens from both inside and outside the cell, through contact or remotely, to advance pathogen replication, to utilize cellular resources, and/or to mitigate immune response. Here, we provide a systematic overview of how and why pathogens interact with and exploit host lipid rafts, as well as the consequences of this interaction for the host, locally and systemically, and for the microbe. We also raise the possibility of modulation of lipid rafts as a therapeutic approach against a variety of infectious agents.

scholarly journals Exit from Host Cells by the Pathogenic Parasite Toxoplasma gondii Does Not Require Motility

2007 ◽  
Vol 7 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Mark D. Lavine ◽  
Gustavo Arrizabalaga
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Host Cells ◽  
Membrane Tension ◽  
Experimental Induction ◽  
Intracellular Parasites ◽  
Artificial Induction ◽  
Host Membrane ◽  
Parasite Motility ◽  
Parasite Egress

ABSTRACTThe process by which the intracellular parasiteToxoplasma gondiiexits its host cell is central to its propagation and pathogenesis. Experimental induction of motility in intracellular parasites results in parasite egress, leading to the hypothesis that egress depends on the parasite's actin-dependent motility. Using a novel assay to monitor egress without experimental induction, we have established that inhibiting parasite motility does not block this process, although treatment with actin-disrupting drugs does delay egress. However, using an irreversible actin inhibitor, we show that this delay is due to the disruption of host cell actin alone, apparently resulting from the consequent loss of membrane tension. Accordingly, by manipulating osmotic pressure, we show that parasite egress is delayed by releasing membrane tension and promoted by increasing it. Therefore, without artificial induction, egress does not depend on parasite motility and can proceed by mechanical rupture of the host membrane.

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