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Virulence Dec 2023The amoeba parasite is the causative agent of human amebiasis, an enteropathic disease affecting millions of people worldwide. This ancient protozoan is an elementary... (Review)
Review
The amoeba parasite is the causative agent of human amebiasis, an enteropathic disease affecting millions of people worldwide. This ancient protozoan is an elementary example of how parasites evolve with humans, e.g. taking advantage of multiple mechanisms to evade immune responses, interacting with microbiota for nutritional and protective needs, utilizing host resources for growth, division, and encystation. These skills of perpetuate the species and incidence of infection. However, in 10% of infected cases, the parasite turns into a pathogen; the host-parasite equilibrium is then disorganized, and the simple lifecycle based on two cell forms, trophozoites and cysts, becomes unbalanced. Trophozoites acquire a virulent phenotype which, when non-controlled, leads to intestinal invasion with the onset of amoebiasis symptoms. Virulent must cross mucus, epithelium, connective tissue and possibly blood. This highly mobile parasite faces various stresses and a powerful host immune response, with oxidative stress being a challenge for its survival. New emerging research avenues and omics technologies target gene regulation to determine human or parasitic factors activated upon infection, their role in virulence activation, and in pathogenesis; this research bears in mind that is a resident of the complex intestinal ecosystem. The goal is to eradicate amoebiasis from the planet, but the parasitic life of is ancient and complex and will likely continue to evolve with humans. Advances in these topics are summarized here.
Topics: Humans; Entamoeba histolytica; Virulence; Ecosystem; Amebiasis; Intestines
PubMed: 36519347
DOI: 10.1080/21505594.2022.2158656 -
PLoS Pathogens May 2020Calcium signaling plays a key role in many essential processes in almost all eukaryotic systems. It is believed that it may also be an important signaling system of the... (Review)
Review
Calcium signaling plays a key role in many essential processes in almost all eukaryotic systems. It is believed that it may also be an important signaling system of the protist parasite Entamoeba histolytica. Motility, adhesion, cytolysis, and phagocytosis/trogocytosis are important steps in invasion and pathogenesis of E. histolytica, and Ca2+ signaling is thought to be associated with these processes leading to tissue invasion. There are a large number of Ca2+-binding proteins (CaBPs) in E. histolytica, and a number of these proteins appear to be associated with different steps in pathogenesis. The genome encodes 27 EF-hand-containing CaBPs in addition to a number of other Ca2+-binding domain/motif-containing proteins, which suggest intricate calcium signaling network in this parasite. Unlike other eukaryotes, a typical calmodulin-like protein has not been seen in E. histolytica. Though none of the CaBPs display sequence similarity with a typical calmodulin, extensive structural similarity has been seen in spite of lack of significant functional overlap with that of typical calmodulins. One of the unique features observed in E. histolytica is the identification of CaBPs (EhCaBP1, EhCaBP3) that have the ability to directly bind actin and modulate actin dynamics. Direct interaction of CaBPs with actin has not been seen in any other system. Pseudopod formation and phagocytosis are some of the processes that require actin dynamics, and some of the amoebic CaBPs (EhC2Pk, EhCaBP1, EhCaBP3, EhCaBP5) participate in this process. None of these E. histolytica CaBPs have any homolog in organisms other than different species of Entamoeba, suggesting a novel Ca2+ signaling pathway that has evolved in this genus.
Topics: Actins; Calcium; Calcium-Binding Proteins; Calmodulin; Entamoeba histolytica; Entamoebiasis; Phagocytosis; Protozoan Proteins
PubMed: 32379809
DOI: 10.1371/journal.ppat.1008214 -
Current Protocols Jan 2022Entamoeba histolytica is a parasitic protozoan and the causative agent of amoebiasis in humans. Amoebiasis has a high incidence of disease, resulting in ∼67,900 deaths...
Entamoeba histolytica is a parasitic protozoan and the causative agent of amoebiasis in humans. Amoebiasis has a high incidence of disease, resulting in ∼67,900 deaths per year, and it poses a tremendous burden of morbidity and mortality in children. Despite its importance, E. histolytica is an understudied parasite. These protocols describe the in vitro growth, maintenance, cryopreservation, genetic manipulation, and cloning of axenic E. histolytica trophozoites. There has been significant progress in genetic manipulation of this organism over the past decade, and these protocols outline the ways in which these advances can be implemented. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Culturing E. histolytica trophozoites Support Protocol 1: Preparation of TYI-S-33 medium Support Protocol 2: Lot testing of Biosate peptone and adult bovine serum for TYI-S-33 medium Basic Protocol 2: Cryopreservation of E. histolytica trophozoites Support Protocol 3: Preparation of cryoprotectant solutions Basic Protocol 3: Transfection of E. histolytica trophozoites with Attractene reagent Basic Protocol 4: Creating clonal lines using limiting dilution Basic Protocol 5: Knockdown of one to two genes with trigger-induced RNA interference Support Protocol 4: Evaluation of RNA interference knockdown with reverse transcriptase PCR Basic Protocol 6: E. histolytica growth curves.
Topics: Adult; Animals; Child; Culture Media; Entamoeba histolytica; Genetic Techniques; Humans; RNA Interference; Trophozoites
PubMed: 35085418
DOI: 10.1002/cpz1.327 -
Frontiers in Cellular and Infection... 2020Lipids are essential players in parasites pathogenesis. In particular, the highly phagocytic trophozoites of , the causative agent of amoebiasis, exhibit a dynamic... (Review)
Review
Lipids are essential players in parasites pathogenesis. In particular, the highly phagocytic trophozoites of , the causative agent of amoebiasis, exhibit a dynamic membrane fusion and fission, in which lipids strongly participate; particularly during the overstated motility of the parasite to reach and attack the epithelia and ingest target cells. Synthesis and metabolism of lipids in this protozoan present remarkable difference with those performed by other eukaryotes. Here, we reviewed the current knowledge on lipids in . Trophozoites synthesize phosphatidylcholine and phosphatidylethanolamine by the Kennedy pathway; and sphingolipids, phosphatidylserine, and phosphatidylinositol, by processes similar to those used by other eukaryotes. However, trophozoites lack enzymes for cholesterol and fatty acids synthesis, which are scavenged from the host or culture medium by specific mechanisms. Cholesterol, a fundamental molecule for the expression of virulence, is transported from the medium into the trophozoites by EhNPC1 and EhNPC2 proteins. Inside cells, lipids are distributed by different pathways, including by the participation of the endosomal sorting complex required for transport (ESCRT), involved in vesicle fusion and fission. Cholesterol interacts with the phospholipid lysobisphosphatidic acid (LBPA) and EhADH, an ALIX family protein, also involved in phagocytosis. In this review, we summarize the known information on phospholipids synthesis and cholesterol transport as well as their metabolic pathways in ; highlighting the mechanisms used by trophozoites to dispose lipids involved in the virulence processes.
Topics: Animals; Cholesterol; Entamoeba histolytica; Entamoebiasis; Fatty Acids; Humans; Lipid Metabolism; Lipids; Phagocytosis; Phospholipids; Protozoan Proteins; Trophozoites; Virulence; Virulence Factors
PubMed: 32211340
DOI: 10.3389/fcimb.2020.00075 -
Frontiers in Cellular and Infection... 2019
Topics: Amebicides; Anisomycin; Asymptomatic Diseases; Drug Discovery; Dysentery, Amebic; Entamoeba histolytica; Flavonoids; Gene Expression Regulation; Humans; Life Cycle Stages; Metabolic Networks and Pathways; Metronidazole; Piperidines; Prodigiosin; Protozoan Proteins; Pyridines; Severity of Illness Index
PubMed: 31338336
DOI: 10.3389/fcimb.2019.00247 -
Current Opinion in Microbiology Dec 2020Entamoeba histolytica, an anaerobic protozoan, is an important global health problem. This parasite has a biphasic life cycle consisting of a dormant cyst stage which is... (Review)
Review
Entamoeba histolytica, an anaerobic protozoan, is an important global health problem. This parasite has a biphasic life cycle consisting of a dormant cyst stage which is environmentally resistant and transmits the infection, and the proliferative trophozoite stage which is motile and causes invasive disease. The stage conversion process remains poorly understood despite being central to amoebic biology. In this review, we will highlight recent progress in our understanding of Entamoeba stage conversion including dissecting transcriptome analysis in development, characterization of transcriptional networks, demonstration of epigenetic regulation, and role of small molecules that regulate Entamoeba development.
Topics: Animals; Entamoeba histolytica; Entamoebiasis; Epigenesis, Genetic; Gene Regulatory Networks; Humans; Life Cycle Stages; Protozoan Proteins
PubMed: 33032142
DOI: 10.1016/j.mib.2020.09.005 -
Frontiers in Cellular and Infection... 2021Protozoan parasites have led to worldwide devastation because of their ability to cause infectious diseases. They have evolved as successful pathogens in part because of... (Review)
Review
Protozoan parasites have led to worldwide devastation because of their ability to cause infectious diseases. They have evolved as successful pathogens in part because of their remarkable and sophisticated ways to evade innate host defenses. This holds true for both intracellular and extracellular parasites that deploy multiple strategies to circumvent innate host defenses for their survival. The different strategies protozoan parasites use include hijacking the host cellular signaling pathways and transcription factors. In particular, the nuclear factor-κB (NF-κB) pathway seems to be an attractive target for different pathogens owing to their central role in regulating prompt innate immune responses in host defense. NF-κB is a ubiquitous transcription factor that plays an indispensable role not only in regulating immediate immune responses against invading pathogens but is also a critical regulator of cell proliferation and survival. The major immunomodulatory components include parasite surface and secreted proteins/enzymes and stimulation of host cells intracellular pathways and inflammatory caspases that directly or indirectly interfere with the NF-κB pathway to thwart immune responses that are directed for containment and/or elimination of the pathogen. To showcase how protozoan parasites exploits the NF-κB signaling pathway, this review highlights recent advances from and other protozoan parasites in contact with host cells that induce outside-in and inside-out signaling to modulate NF-κB in disease pathogenesis and survival in the host.
Topics: Animals; Entamoeba histolytica; Immunity, Innate; NF-kappa B; Parasites; Signal Transduction
PubMed: 34595137
DOI: 10.3389/fcimb.2021.748404 -
Frontiers in Cellular and Infection... 2018In eukaryotic cells, the life cycle of mRNA molecules is modulated in response to environmental signals and cell-cell communication in order to support cellular... (Review)
Review
In eukaryotic cells, the life cycle of mRNA molecules is modulated in response to environmental signals and cell-cell communication in order to support cellular homeostasis. Capping, splicing and polyadenylation in the nucleus lead to the formation of transcripts that are suitable for translation in cytoplasm, until mRNA decay occurs in P-bodies. Although pre-mRNA processing and degradation mechanisms have usually been studied separately, they occur simultaneously and in a coordinated manner through protein-protein interactions, maintaining the integrity of gene expression. In the past few years, the availability of the genome sequence of , the protozoan parasite responsible for human amoebiasis, coupled to the development of the so-called "omics" technologies provided new opportunities for the study of mRNA processing and turnover in this pathogen. Here, we review the current knowledge about the molecular basis for splicing, 3' end formation and mRNA degradation in amoeba, which suggest the conservation of events related to mRNA life throughout evolution. We also present the functional characterization of some key proteins and describe some interactions that indicate the relevance of cooperative regulatory events for gene expression in this human parasite.
Topics: Amebiasis; Animals; Entamoeba histolytica; Evolution, Molecular; Humans; Polyadenylation; Protozoan Proteins; RNA Precursors; RNA Splicing; RNA Stability; RNA, Messenger
PubMed: 29971219
DOI: 10.3389/fcimb.2018.00199 -
Clinical Microbiology Reviews Oct 1992Entamoeba histolytica, the causative agent of amebiasis, was first described in 1875. Although a large number of people throughout the world are infected with this... (Review)
Review
Entamoeba histolytica, the causative agent of amebiasis, was first described in 1875. Although a large number of people throughout the world are infected with this organism, only a small percentage will develop clinical symptoms. Morbidity and mortality due to E. histolytica vary from area to area and person to person. Recent findings have suggested that there are pathogenic and nonpathogenic strains of E. histolytica that can be differentiated by isoenzyme (zymodeme) analysis, monoclonal antibodies, and DNA probes. Whether pathogenicity is a genotypic trait or can be changed by environmental influences has not been resolved. Exchange of genetic material between strains of amebae can influence zymodeme patterns. Currently, detection of E. histolytica infections depends on examinations for ova and parasites and on serologic tests; however, the development of monoclonal antibodies and DNA probes specific for pathogenic zymodemes may be beneficial for clinical laboratory testing and therapeutic decisions when approved tests become available. A better understanding of the mechanisms of pathogenicity at the molecular level is evolving and should promote the development of vaccines and better target selection for therapeutic agents.
Topics: Animals; Entamoeba histolytica; Entamoebiasis; Forecasting; Humans; Male
PubMed: 1423215
DOI: 10.1128/CMR.5.4.356 -
Annual Review of Microbiology 2014Entamoeba histolytica is the third-leading cause of parasitic mortality globally. E. histolytica infection generally does not cause symptoms, but the parasite has potent... (Review)
Review
Entamoeba histolytica is the third-leading cause of parasitic mortality globally. E. histolytica infection generally does not cause symptoms, but the parasite has potent pathogenic potential. The origins, benefits, and triggers of amoebic virulence are complex. Amoebic pathogenesis entails depletion of the host mucosal barrier, adherence to the colonic lumen, cytotoxicity, and invasion of the colonic epithelium. Parasite damage results in colitis and, in some cases, disseminated disease. Both host and parasite genotypes influence the development of disease, as do the regulatory responses they govern at the host-pathogen interface. Host environmental factors determine parasite transmission and shape the colonic microenvironment E. histolytica infects. Here we highlight research that illuminates novel links between host, parasite, and environmental factors in the regulation of E. histolytica virulence.
Topics: Animals; Entamoeba histolytica; Entamoebiasis; Humans; Protozoan Proteins; Virulence
PubMed: 25002094
DOI: 10.1146/annurev-micro-091313-103550