scholarly journals Autophagy Activated by Peroxiredoxin of Entamoeba histolytica

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2462
Author(s):  
Xia Li ◽  
Yuhan Zhang ◽  
Yanqing Zhao ◽  
Ke Qiao ◽  
Meng Feng ◽  
...  
Keyword(s):  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Functional Domain ◽  
Intestinal Protozoan ◽  
Raw264.7 Macrophages ◽  
Evolutionarily Conserved ◽  
Amoebic Colitis ◽  
Dependent Cell ◽  
Cellular Components

Autophagy, an evolutionarily conserved mechanism to remove redundant or dangerous cellular components, plays an important role in innate immunity and defense against pathogens, which, in turn, can regulate autophagy to establish infection within a host. However, for Entamoeba histolytica, an intestinal protozoan parasite causing human amoebic colitis, the interaction with the host cell autophagy mechanism has not been investigated. In this study, we found that E. histolytica peroxiredoxin (Prx), an antioxidant enzyme critical for parasite survival during the invasion of host tissues, could activate autophagy in macrophages. The formation of autophagosomes in macrophages treated with recombinant Prx of E. histolytica for 24 h was revealed by immunofluorescence and immunoblotting in RAW264.7 cells and in mice. Prx was cytotoxic for RAW264.7 macrophages after 48-h treatment, which was partly attributed to autophagy-dependent cell death. RNA interference experiments revealed that Prx induced autophagy mostly through the toll-like receptor 4 (TLR4)–TIR domain-containing adaptor-inducing interferon (TRIF) pathway. The C-terminal part of Prx comprising 100 amino acids was the key functional domain to activate autophagy. These results indicated that Prx of E. histolytica could induce autophagy and cytotoxic effects in macrophages, revealing a new pathogenic mechanism activated by E. histolytica in host cells.

scholarly journals Roles of Cell Adhesion and Cytoskeleton Activity in Entamoeba histolytica Pathogenesis: a Delicate Balance

2005 ◽  
Vol 73 (3) ◽  
pp. 1771-1778 ◽  
Author(s):  
Paulo Tavares ◽  
Marie-Christine Rigothier ◽  
Huot Khun ◽  
Pascal Roux ◽  
Michel Huerre ◽  
...  
Keyword(s):  
Entamoeba Histolytica ◽  
Myosin Ii ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Hepatic Tissue ◽  
Surface Adhesion ◽  
Amoebic Colitis ◽  
Parasite Motility ◽  
Focal Structures ◽  
Actomyosin Cytoskeleton

ABSTRACT The protozoan parasite Entamoeba histolytica colonizes the human large bowel. Invasion of the intestinal epithelium causes amoebic colitis and opens the route for amoebic liver abscesses. The parasite relies on its dynamic actomyosin cytoskeleton and on surface adhesion molecules for dissemination in the human tissues. Here we show that the galactose/N-acetylgalactosamine (Gal/GalNAc) lectin clusters in focal structures localized in the region of E. histolytica that contacts monolayers of enterocytes. Disruption of myosin II activity impairs the formation of these structures and renders the trophozoites avirulent for liver abscess development. Production of the cytoplasmic domain of the E. histolytica Gal/GalNAc lectin in engineered trophozoites causes reduced adhesion to enterocytes. Intraportal delivery of these parasites to the liver leads to the formation of a large number of small abscesses with disorganized morphology that are localized in the vicinity of blood vessels. The data support a model for invasion in which parasite motility is essential for establishment of infectious foci, while the adhesion to host cells modulates the distribution of trophozoites in the liver and their capacity to migrate in the hepatic tissue.

scholarly journals Near-chromosome level genome assembly reveals ploidy diversity and plasticity in the intestinal protozoan parasite Entamoeba histolytica

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Tetsuro Kawano-Sugaya ◽  
Shinji Izumiyama ◽  
Yasuaki Yanagawa ◽  
Yumiko Saito-Nakano ◽  
Koji Watanabe ◽  
...  
Keyword(s):  
Entamoeba Histolytica ◽  
Evolutionary Biology ◽  
Regulation Of Gene Expression ◽  
Protozoan Parasite ◽  
Model Organisms ◽  
Intestinal Protozoan ◽  
Disease Symptoms ◽  
Veterinary Importance ◽  
Reference Genomes ◽  
Chromosome Level

Abstract Background Amoebozoa is a eukaryotic supergroup composed of unicellular and multicellular amoebic protozoa (e.g. Acanthamoeba, Dictyostelium, and Entamoeba). They are model organisms for studies in cellular and evolutionary biology and are of medical and veterinary importance. Despite their importance, Amoebozoan genome organization and genetic diversity remain poorly studied due to a lack of high-quality reference genomes. The slime mold Dictyostelium discoideum is the only Amoebozoan species whose genome is available at the chromosome-level. Results Here, we provide a near-chromosome-level assembly of the Entamoeba histolytica genome, the second semi-completed Amoebozoan genome. The availability of this improved genome allowed us to discover inter-strain heterogeneity in ploidy at the near-chromosome or sub-chromosome level among 11 clinical isolates and the reference strain. Furthermore, we observed ploidy-independent regulation of gene expression, contrary to what is observed in other organisms, where RNA levels are affected by ploidy. Conclusions Our findings offer new insights into Entamoeba chromosome organization, ploidy, transcriptional regulation, and inter-strain variation, which will help to further decipher observed spectrums of virulence, disease symptoms, and drug sensitivity of E. histolytica isolates.

scholarly journals A Sequential Model of Host Cell Killing and Phagocytosis byEntamoeba histolytica

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Adam Sateriale ◽  
Christopher D. Huston
Keyword(s):  
Host Cell ◽  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Cell Killing ◽  
Host Cells ◽  
Strongly Correlated ◽  
Sequential Model ◽  
Recent Advances

The protozoan parasiteEntamoeba histolyticais responsible for invasive intestinal and extraintestinal amebiasis. The virulence ofEntamoeba histolyticais strongly correlated with the parasite's capacity to effectively kill and phagocytose host cells. The process by which host cells are killed and phagocytosed follows a sequential model of adherence, cell killing, initiation of phagocytosis, and engulfment. This paper presents recent advances in the cytolytic and phagocytic processes ofEntamoeba histolyticain context of the sequential model.

scholarly journals Knockdown of Five Genes Encoding Uncharacterized Proteins Inhibits Entamoeba histolytica Phagocytosis of Dead Host Cells

2016 ◽  
Vol 84 (4) ◽  
pp. 1045-1053 ◽  
Author(s):  
Adam Sateriale ◽  
Peter Miller ◽  
Christopher D. Huston
Keyword(s):  
Host Cell ◽  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Data Set ◽  
Feed Forward ◽  
Content Type ◽  
Genes Encoding ◽  
Relative Specificity ◽  
Cell Engulfment

Entamoeba histolyticais the protozoan parasite that causes invasive amebiasis, which is endemic to many developing countries and characterized by dysentery and liver abscesses. The virulence ofE. histolyticacorrelates with the degree of host cell engulfment, or phagocytosis, andE. histolyticaphagocytosis alters amebic gene expression in a feed-forward manner that results in an increased phagocytic ability. Here, we used a streamlined RNA interference screen to silence the expression of 15 genes whose expression was upregulated in phagocyticE. histolyticatrophozoites to determine whether these genes actually function in the phagocytic process. When five of these genes were silenced, amebic strains with significant decreases in the ability to phagocytose apoptotic host cells were produced. Phagocytosis of live host cells, however, was largely unchanged, and the defects were surprisingly specific for phagocytosis. Two of the five encoded proteins, which we namedE. histolyticaILWEQ (EhILWEQ) andE. histolyticaBAR (EhBAR), were chosen for localization via SNAP tag labeling and localized to the site of partially formed phagosomes. Therefore, both EhILWEQ and EhBAR appear to contribute toE. histolyticavirulence through their function in phagocytosis, and the large proportion (5/15 [33%]) of gene-silenced strains with a reduced ability to phagocytose host cells validates the previously published microarray data set demonstrating feed-forward control ofE. histolyticaphagocytosis. Finally, although only limited conclusions can be drawn from studies using the virulence-deficient G3Entamoebastrain, the relative specificity of the defects induced for phagocytosis of apoptotic cells but not healthy cells suggests that cell killing may play a rate-limiting role in the process ofEntamoeba histolyticahost cell engulfment.

scholarly journals Genome-Wide Analysis of Known and Potential Tetraspanins in Entamoeba histolytica

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 885 ◽  
Author(s):  
Tomii ◽  
Santos ◽  
Nozaki
Keyword(s):  
Entamoeba Histolytica ◽  
Sequence Similarity ◽  
Protozoan Parasite ◽  
Intercellular Signaling ◽  
Intestinal Protozoan ◽  
Membrane Protein Complex ◽  
Genome Wide Analysis ◽  
Protein Complex Formation ◽  
Genome Wide ◽  
Similarity Searches

Tetraspanins are membrane proteins involved in intra- and/or intercellular signaling, and membrane protein complex formation. In some organisms, their role is associated with virulence and pathogenesis. Here, we investigate known and potential tetraspanins in the human intestinal protozoan parasite Entamoeba histolytica. We conducted sequence similarity searches against the proteome data of E. histolytica and newly identified nine uncharacterized proteins as potential tetraspanins in E. histolytica. We found three subgroups within known and potential tetraspanins, as well as subgroup-associated features in both their amino acid and nucleotide sequences. We also examined the subcellular localization of a few representative tetraspanins that might be potentially related to pathogenicity. The results in this study could be useful resources for further understanding and downstream analyses of tetraspanins in Entamoeba.

scholarly journals Persistent abdominal pain of a middle aged old female– Think of Amoebic Colitis

2019 ◽  
Vol 7 (1) ◽  
pp. 58-60
Author(s):  
Chowdhury Rifat Niger ◽  
Chowdhury Akram Uz Zaman ◽  
Raj Chowdhury ◽  
Tamzeed Hossain ◽  
Tania Mahbub ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Gastrointestinal Disorder ◽  
Severe Abdominal Pain ◽  
Middle Aged ◽  
Amebic Colitis ◽  
Underdeveloped Countries ◽  
Persistent Abdominal Pain ◽  
Amoebic Colitis

Amebic colitis, also known as amebiasis, is a gastrointestinal disorder caused by invasion of the intestine by the protozoan parasite, Entamoeba histolytica. Although primarily a disease found in underdeveloped countries, this condition may exist in patients who have recently travelled these area. Obtaining an accurate history and testing are crucial for correctly diagnosing and treating amebic colitis. Here we are reporting a case of Amoebic Colitis who has presented with severe abdominal pain and diarrhoea. Bangladesh Crit Care J March 2019; 7(1): 58-60

scholarly journals The Intestinal Protozoan Parasite Entamoeba histolytica Contains 20 Cysteine Protease Genes, of Which Only a Small Subset Is Expressed during In Vitro Cultivation

2003 ◽  
Vol 2 (3) ◽  
pp. 501-509 ◽  
Author(s):  
Iris Bruchhaus ◽  
Brendan J. Loftus ◽  
Neil Hall ◽  
Egbert Tannich
Keyword(s):  
Entamoeba Histolytica ◽  
Cysteine Protease ◽  
Cathepsin L ◽  
Protozoan Parasite ◽  
Cysteine Proteases ◽  
Small Subset ◽  
In Vitro Cultivation ◽  
Intestinal Protozoan ◽  
Parasite Life Cycle

ABSTRACT Cysteine proteases are known to be important pathogenicity factors of the protozoan parasite Entamoeba histolytica. So far, a total of eight genes coding for cysteine proteases have been identified in E. histolytica, two of which are absent in the closely related nonpathogenic species E. dispar. However, present knowledge is restricted to enzymes expressed during in vitro cultivation of the parasite, which might represent only a subset of the entire repertoire. Taking advantage of the current E. histolytica genome-sequencing efforts, we analyzed databases containing more than 99% of all ameba gene sequences for the presence of cysteine protease genes. A total of 20 full-length genes was identified (including all eight genes previously reported), which show 10 to 86% sequence identity. The various genes obviously originated from two separate ancestors since they form two distinct clades. Despite cathepsin B-like substrate specificities, all of the ameba polypeptides are structurally related to cathepsin L-like enzymes. None of the previously described enzymes but 7 of the 12 newly identified proteins are unique compared to cathepsins of higher eukaryotes in that they are predicted to have transmembrane or glycosylphosphatidylinositol anchor attachment domains. Southern blot analysis revealed that orthologous sequences for all of the newly identified proteases are present in E. dispar. Interestingly, the majority of the various cysteine protease genes are not expressed in E. histolytica or E. dispar trophozoites during in vitro cultivation. Therefore, it is likely that at least some of these enzymes are required for infection of the human host and/or for completion of the parasite life cycle.

Molecular-based diagnosis of Entamoeba histolytica infection

1999 ◽  
Vol 1 (9) ◽  
pp. 1-11 ◽  
Author(s):  
Christopher D. Huston ◽  
Rashidul Haque ◽  
William A. Petri
Keyword(s):  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Test Methods ◽  
Molecular Techniques ◽  
Test Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Entamoeba Dispar ◽  
Isoenzyme Analysis ◽  
Amoebic Colitis ◽  
Pcr Method

Infection with Entamoeba histolytica, the protozoan parasite that causes amoebic colitis and liver abscess, results in 34 million to 50 million symptomatic cases of amoebiasis (all illnesses caused by E. histolytica, including amoebic dysentery) worldwide each year, causing 40 thousand to 100 thousand deaths annually. As a result of accruing biochemical, genetic and immunological data, E. histolytica was re-defined in 1993 to recognise the existence of two morphologically identical but genetically distinct human parasites: E. histolytica, the aetiological agent of invasive intestinal and extraintestinal amoebiasis, and Entamoeba dispar, a non-pathogenic intestinal parasite. Because microscopy is unable to distinguish between these two organisms, it should no longer be relied upon to diagnose amoebiasis. Sensitive and specific molecular techniques that are able to distinguish E. histolytica from E. dispar have been developed recently; they include (1) the detection of an E. histolytica antigen using an enzyme-linked immunosorbent assay (ELISA), (2) the use of the polymerase chain reaction (PCR) to amplify amoebic DNA, and (3) the culture of stool samples followed by isoenzyme analysis. Of these three test methods, only antigen detection using ELISA can be performed rapidly and easily, making it the diagnostic test method of choice for clinical use in the developing world, where the morbidity and mortality caused by E. histolytica are greatest. However, the PCR method is a powerful tool for the genetic typing of different amoebic strains. Together these two methods should result in both improved clinical diagnosis and treatment of amoebiasis, and a greater understanding of the epidemiology of E. histolytica. Such knowledge will not only assist public health efforts to control amoebiasis, but also facilitate the careful testing of the anti-amoebic vaccines that are currently being developed.

scholarly journals A Novel TLR4-Binding Domain of Peroxiredoxin From Entamoeba histolytica Triggers NLRP3 Inflammasome Activation in Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Xia Li ◽  
Meng Feng ◽  
Yanqing Zhao ◽  
Yuhan Zhang ◽  
Ruixue Zhou ◽  
...  
Keyword(s):  
Entamoeba Histolytica ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Alternative Pathway ◽  
Host Cells ◽  
Cell Contact ◽  
Inflammasome Activation ◽  
Functional Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Cell Cell

Macrophages promote early host responses to infection by releasing pro-inflammatory cytokines, and they are crucial to combat amoebiasis, a disease affecting millions of people worldwide. Macrophages elicit pro-inflammatory responses following direct cell/cell interaction of Entamoeba histolytica, inducing NLRP3 inflammasome activation with high-output IL-1β/IL-18 secretion. Here, we found that trophozoites could upregulate peroxiredoxins (Prx) expression and abundantly secrete Prxs when encountering host cells. The C-terminal of Prx was identified as the key functional domain in promoting NLRP3 inflammasome activation, and a recombinant C-terminal domain could act directly on macrophage. The Prxs derived from E. histolytica triggered toll-like receptor 4-dependent activation of NLRP3 inflammasome in a cell/cell contact-independent manner. Through genetic, immunoblotting or pharmacological inhibition methods, NLRP3 inflammasome activation was induced through caspase-1-dependent canonical pathway. Our data suggest that E. histolytica Prxs had stable and durable cell/cell contact-independent effects on macrophages following abundantly secretion during invasion, and the C-terminal of Prx was responsible for activating NLRP3 inflammasome in macrophages. This new alternative pathway may represent a potential novel therapeutic approach for amoebiasis, a global threat to millions.

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