ABSTRACT
Cell migration modes can vary, depending on a number of environmental and intracellular factors. The high motility of the pathogenic amoeba Entamoeba histolytica is a decisive factor in its ability to cross the human colonic barrier. We used quantitative live imaging techniques to study the migration of this parasite on fibronectin, a key tissue component. Entamoeba histolytica amoebae on fibronectin contain abundant podosome-like structures. By using a laminar flow chamber, we determined that the adhesion forces generated on fibronectin were twice those on non-coated glass. When migrating on fibronectin, elongated amoeboid cells converted into fan-shaped cells characterized by the presence of a dorsal column of F-actin and a broad cytoplasmic extension at the front. The fan shape depended on the Arp2/3 complex, and the amoebae moved laterally and more slowly. Intracellular measurements of physical variables related to fluid dynamics revealed that cytoplasmic pressure gradients were weaker within fan-shaped cells; hence, actomyosin motors might be less involved in driving the cell body forward. We also found that the Rho-associated coiled-coil containing protein kinase regulated podosome dynamics. We conclude that E. histolytica spontaneously changes its migration mode as a function of the substrate composition. This adaptive ability might favour E. histolytica's invasion of human colonic tissue. By combining microfluidic experiments, mechanical modelling, and image analysis, our work also introduces a computational pipeline for the study of cell migration.
Subject(s)
Cell Movement , Entamoeba histolytica , Fibronectins , Entamoeba histolytica/metabolism , Entamoeba histolytica/physiology , Fibronectins/metabolism , Humans , Cell Movement/physiology , Entamoebiasis/parasitology , Entamoebiasis/metabolism , Actins/metabolism , Podosomes/metabolism , Cell Adhesion/physiology , Protozoan Proteins/metabolismABSTRACT
Entamoeba histolytica is a protozoan parasite and the causative agent of amoebiasis in humans. This amoeba invades human tissues by taking advantage of its actin-rich cytoskeleton to move, enter the tissue matrix, kill and phagocyte the human cells. During tissue invasion, E. histolytica moves from the intestinal lumen across the mucus layer and enters the epithelial parenchyma. Faced with the chemical and physical constraints of these diverse environments, E. histolytica has developed sophisticated systems to integrate internal and external signals and to coordinate cell shape changes and motility. Cell signalling circuits are driven by interactions between the parasite and extracellular matrix, combined with rapid responses from the mechanobiome in which protein phosphorylation plays an important role. To understand the role of phosphorylation events and related signalling mechanisms, we targeted phosphatidylinositol 3-kinases followed by live cell imaging and phosphoproteomics. The results highlight 1150 proteins, out of the 7966 proteins within the amoebic proteome, as members of the phosphoproteome, including signalling and structural molecules involved in cytoskeletal activities. Inhibition of phosphatidylinositol 3-kinases alters phosphorylation in important members of these categories; a finding that correlates with changes in amoeba motility and morphology, as well as a decrease in actin-rich adhesive structures.
Subject(s)
Amebiasis , Entamoeba histolytica , Humans , Actins/metabolism , Entamoeba histolytica/metabolism , Actin Cytoskeleton/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protozoan Proteins/metabolismABSTRACT
Entamoeba histolytica is the etiological agent of amebiasis in humans. This ameba parasite resides as a commensal in the intestine where it shares intestinal resources with the bacterial microbiome. In the intestinal ecosystem, the ameba encysts and eventually develops disease by invading the tissues. E. histolytica possesses cell surface receptors for the proper sensing of signals involved in encystation or sustaining parasite interaction with bacteria and human cells. Among those receptors are the Gal/GalNAc lectin, G protein-coupled receptors, and transmembrane kinases. In addition there are recently discovered, promising proteins, including orthologs of Toll-type receptors and ß trefoil lectins. These proteins trigger a wide variety of signal transduction pathways; however, most of the players involved in the signaling pathways evoked in this parasite are unknown. This review provides an overview of amoebic receptors and their role in encystation, adherence to bacteria or human cells, as well as the reported intracellular signal transduction processes that they can trigger. This knowledge is essential for understanding the lifestyle of E. histolytica and its cytopathic effect on bacteria and human cells that are responsible for infection.
Subject(s)
Bacteria/metabolism , Entamoeba histolytica/growth & development , Entamoeba histolytica/metabolism , Entamoebiasis/parasitology , Animals , Bacteria/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Entamoeba histolytica/genetics , Entamoebiasis/genetics , Entamoebiasis/metabolism , Humans , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Signal TransductionABSTRACT
Entamoeba histolytica is the causative agent of amebiasis, an infectious disease targeting the intestine and the liver in humans. Two types of intestinal infection are caused by this parasite: silent infection, which occurs in the majority of cases, and invasive disease, which affects 10% of infected persons. To understand the intestinal pathogenic process, several in vitro models, such as cell cultures, human tissue explants or human intestine xenografts in mice, have been employed. Nevertheless, our knowledge on the early steps of amebic intestinal infection and the molecules involved during human-parasite interaction is scarce, in part due to limitations in the experimental settings. In the present work, we took advantage of tissue engineering approaches to build a three-dimensional (3D)-intestinal model that is able to replicate the general characteristics of the human colon. This system consists of an epithelial layer that develops tight and adherens junctions, a mucus layer and a lamina propria-like compartment made up of collagen containing macrophages and fibroblast. By means of microscopy imaging, omics assays and the evaluation of immune responses, we show a very dynamic interaction between E. histolytica and the 3D-intestinal model. Our data highlight the importance of several virulence markers occurring in patients or in experimental models, but they also demonstrate the involvement of under described molecules and regulatory factors in the amoebic invasive process.
Subject(s)
Amebiasis/parasitology , Entamoeba histolytica/pathogenicity , Intestines/microbiology , Intestines/pathology , Models, Anatomic , Amebiasis/immunology , Dysentery, Amebic/pathology , Entamoeba histolytica/immunology , Host-Parasite Interactions , Humans , Inflammation , Microscopy, Confocal , VirulenceABSTRACT
The amoeba parasite Entamoeba histolytica interacts with the microbiota within the intestine. Enterobacteria are the major source of energy for this parasite. Here, we highlight that the interplay between enterobacteria and E. histolytica is also important for parasite survival during inflammatory stresses and for the success of amoebic infection.
Subject(s)
Entamoeba histolytica/metabolism , Entamoebiasis/metabolism , Enterobacteriaceae/metabolism , Intestines/parasitology , Cell Movement , Cytoskeleton/metabolism , Entamoeba histolytica/parasitology , Entamoebiasis/immunology , Host-Parasite Interactions/physiology , Humans , Intestines/microbiology , Microbiota , Oxidative Stress , Phagocytosis , Protein Domains , Protozoan Proteins/chemistry , Protozoan Proteins/metabolismABSTRACT
Actin is one of the most conserved, abundant, and ubiquitous proteins in all eukaryotes characterised to date. Posttranslation modifications of actin modify the organisation of the actin-rich cytoskeleton. In particular, chemical modifications of actin's amino-terminal region determine how filamentous actin is organised into scaffolds. After assuming that protein modifications account for the multiple functional activities exerted by the single actin in Entamoeba histolytica, we profiled posttranslational modifications of this protein. Acetylation (on 21 different amino acids) was the most abundant modification, followed by phosphorylation. Furthermore, the glycine residue at Position 2 in E. histolytica's actin (Gly2, not found in most other eukaryotic actins) was found to be acetylated. The impact of Gly2 on the amoeba's life cycle and pathogenicity was then assessed in mutagenesis experiments. We found that Gly2 was necessary for cell morphology and division, parasite-host cell adhesion, and host invasion in an in vitro model of amoebic human infection.
Subject(s)
Actin Cytoskeleton/metabolism , Entamoeba histolytica/metabolism , Protozoan Proteins/metabolism , Acetylation , Cell Adhesion/physiology , Humans , Phosphorylation , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Processing, Post-Translational , Protozoan Proteins/chemistry , Protozoan Proteins/geneticsABSTRACT
The protozoan parasite Entamoeba histolytica is the microbial agent of amoebiasis - an infection that is endemic worldwide and is associated with high morbidity and mortality rates. As the disease develops, virulent E. histolytica deplete the mucus layer, interact with the intestinal epithelium, and then degrade the colonic mucosa and disrupt the extracellular matrix (ECM). Our research demonstrated that virulent parasites with an invasive phenotype display rapid, highly specific changes in their transcriptome (notably for essential factors involved in carbohydrate metabolism and the processing of glycosylated residues). Moreover, combined activation of parasite and host lytic enzymes leads to the destruction of the intestinal parenchyma. Together, these enzymes degrade the mucus layer and the ECM, and trigger the inflammatory response essential to the development of amoebiasis.
Subject(s)
Amebiasis/parasitology , Entamoeba histolytica/pathogenicity , Host-Parasite Interactions , Intestinal Mucosa/physiology , Intestinal Mucosa/parasitology , Signal Transduction , Amebiasis/physiopathology , Animals , Colon/cytology , Colon/parasitology , Genome, Bacterial , Humans , Inflammation , TranscriptomeABSTRACT
Entamoeba histolytica, the causative agent of amoebiasis, is a protozoan parasite characterised by its amoeboid motility, which is essential to its survival and invasion of the human host. Elucidating the molecular mechanisms leading to invasion of human tissues by E. histolytica requires a quantitative understanding of how its cytoskeleton deforms and tailors its mode of migration to the local microenvironment. Here we review the wide range of methods available to extract biophysical information from amoeboid cells, from interventional techniques to computational modelling approaches, and discuss how recent developments in bioimaging and bioimage informatics can complement our understanding of cellular morphodynamics at the intracellular level.
Subject(s)
Amebiasis/parasitology , Entamoeba histolytica/physiology , Models, Biological , Computer Simulation , Host-Parasite Interactions , Humans , Microscopy, Atomic Force , Microscopy, Confocal , Microscopy, Phase-Contrast , Movement/physiologyABSTRACT
The development of amoebiasis is influenced by the expression of the lysine and glutamic acid rich protein 1 (KERP1), a virulence factor involved in Entamoeba histolytica adherence to human cells. Up to date, it is unknown how the protein transits the parasite cytoplasm towards the plasma membrane, specially because this organism lacks a well-defined endoplasmic reticulum (ER) and Golgi apparatus. In this work we demonstrate that KERP1 is present at the cell surface and in intracellular vesicles which traffic in a pathway that is independent of the ER-Golgi anterograde transport. The intracellular displacement of vesicles enriched in KERP1 relies on the actin-rich cytoskeleton activities. KERP1 is also present in externalized vesicles deposited on the surface of human cells. We further report the interactome of KERP1 with its association to endomembrane components and lipids. The model for KERP1 traffic here proposed hints for the first time elements of the endocytic and exocytic paths of E. histolytica.
Subject(s)
Entamoeba histolytica/metabolism , Protozoan Proteins/metabolism , Actin Cytoskeleton/metabolism , Cell Membrane/metabolism , Cytoplasm/metabolism , Cytoplasm/ultrastructure , Entamoeba histolytica/ultrastructure , Protein Transport , Transport Vesicles/metabolism , Virulence Factors/metabolismABSTRACT
Small GTPases are signalling molecules that regulate important cellular processes. GTPases are deactivated by GTPase-activating proteins (GAPs). While human GAPs have been intensively studied, no GAP has yet been characterized in Entamoeba histolytica. In this study, we identified and characterized a novel nucleocytoplasmic RhoGAP in E. histolytica termed EhRhoGAPnc. In silico analyses of the domain structure revealed a previously undescribed peptide region within the carboxy-terminal region of EhRhoGAPnc capable of interacting with phosphatidic acid and phosphatidylinositol 3,5-bisphosphate. The full structural GAP domain showed increase GAP activity compared with the minimum region able to display GAP activity, as analysed both by experimental assays and molecular dynamics simulations. Furthermore, we identified amino acid residues that promote interactions between EhRhoGAPnc and its target GTPases EhRacC and EhRacD. Immunofluorescence studies revealed that EhRhoGAPnc colocalized with EhRacC and EhRacD during uroid formation but not during erythrophagocytosis. Interestingly, during erythrophagocytosis of red blood cells, EhRhoGAPnc colocalized with phosphatidic acid and phosphatidylinositol 3,5-bisphosphate. Overexpression of EhRhoGAPnc in E. histolytica led to inhibition of actin adhesion plate formation, migration, adhesion of E. histolytica to MDCK cells and consequently to an impairment of the cytopathic activity.
Subject(s)
Entamoeba histolytica/pathogenicity , GTPase-Activating Proteins/physiology , Protozoan Proteins/physiology , rac GTP-Binding Proteins/metabolism , Amino Acid Sequence , Binding Sites , Cell Nucleus/metabolism , Conserved Sequence , Cytoplasm/metabolism , Entamoeba histolytica/enzymology , Erythrocytes/parasitology , GTPase-Activating Proteins/chemistry , Humans , Molecular Dynamics Simulation , Phagocytosis , Protein Transport , Protozoan Proteins/chemistryABSTRACT
Investigations of human parasitic diseases depend on the availability of appropriate in vivo animal models and ex vivo experimental systems, and are particularly difficult for pathogens whose exclusive natural hosts are humans, such as Entamoeba histolytica, the protozoan parasite responsible for amoebiasis. This common infectious human disease affects the intestine and liver. In the liver sinusoids E. histolytica crosses the endothelium and penetrates into the parenchyma, with the concomitant initiation of inflammatory foci and subsequent abscess formation. Studying factors responsible for human liver infection is hampered by the complexity of the hepatic environment and by the restrictions inherent to the use of human samples. Therefore, we built a human 3D-liver in vitro model composed of cultured liver sinusoidal endothelial cells and hepatocytes in a 3D collagen-I matrix sandwich. We determined the presence of important hepatic markers and demonstrated that the cell layers function as a biological barrier. E. histolytica invasion was assessed using wild-type strains and amoebae with altered virulence or different adhesive properties. We showed for the first time the dependence of endothelium crossing upon amoebic Gal/GalNAc lectin. The 3D-liver model enabled the molecular analysis of human cell responses, suggesting for the first time a crucial role of human galectins in parasite adhesion to the endothelial cells, which was confirmed by siRNA knockdown of galectin-1. Levels of several pro-inflammatory cytokines, including galectin-1 and -3, were highly increased upon contact of E. histolytica with the 3D-liver model. The presence of galectin-1 and -3 in the extracellular medium stimulated pro-inflammatory cytokine release, suggesting a further role for human galectins in the onset of the hepatic inflammatory response. These new findings are relevant for a better understanding of human liver infection by E. histolytica.
Subject(s)
Carcinoma, Hepatocellular/parasitology , Entamoeba histolytica/pathogenicity , Entamoebiasis/parasitology , Galectin 1/metabolism , Galectin 3/metabolism , Liver Neoplasms/parasitology , Liver/parasitology , Cell Adhesion , Cell Culture Techniques , Cells, Cultured , Cytokines/genetics , Cytokines/metabolism , Fluorescent Antibody Technique , Galectin 1/genetics , Galectin 3/genetics , Humans , Immunoblotting , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Real-Time Polymerase Chain Reaction , VirulenceABSTRACT
Adhesion to cells, cytotoxicity and proteolysis are functions required for virulence and pathogenicity of Entamoeba histolytica. However, there was no correlation between these in vitro functions and the early elimination of non-pathogenic E. dispar and non-virulent E. histolytica (nvEh) in experimental amoebic liver abscesses developed in hamsters. Thus, additional functions may be involved in amoebic pathogenicity and virulence. In the present study, an integral experimental assessment, including innovative technologies for analyses of amoebal pathophysiology, cell biology, biochemistry and transcriptomics, was carried out to elucidate whether other cellular processes are involved in amoebal pathogenicity and virulence. In comparison with virulent E. histolytica, the data indicated that the main reasons for the early clearance of nvEh from hamster liver are decreased intracellular H2 O2 detoxification rate and deficient heat shock protein expression, whereas for E. dispar, it is a relatively lower capacity for O2 reduction. Therefore, maintenance of an intracellular hypoxic environment combined with the induction of an adequate parasite response to oxidative stress are essential requirements for Entamoeba survival in the liver, and therefore for pathogenicity.
Subject(s)
Entamoeba histolytica/pathogenicity , Heat-Shock Response , Host-Pathogen Interactions , Oxidative Stress , Animals , Cell Survival , Cricetinae , Liver/parasitology , Liver/pathology , VirulenceABSTRACT
Entamoeba histolytica is the pathogenic amoeba responsible for amoebiasis, an infectious disease targeting human tissues. Amoebiasis arises when virulent trophozoites start to destroy the muco-epithelial barrier by first crossing the mucus, then killing host cells, triggering inflammation and subsequently causing dysentery. The main goal of this study was to analyse pathophysiology and gene expression changes related to virulent (i.e. HM1:IMSS) and non-virulent (i.e. Rahman) strains when they are in contact with the human colon. Transcriptome comparisons between the two strains, both in culture conditions and upon contact with human colon explants, provide a global view of gene expression changes that might contribute to the observed phenotypic differences. The most remarkable feature of the virulent phenotype resides in the up-regulation of genes implicated in carbohydrate metabolism and processing of glycosylated residues. Consequently, inhibition of gene expression by RNA interference of a glycoside hydrolase (ß-amylase absent from humans) abolishes mucus depletion and tissue invasion by HM1:IMSS. In summary, our data suggest a potential role of carbohydrate metabolism in colon invasion by virulent E. histolytica.
Subject(s)
Colon/parasitology , Dysentery, Amebic/parasitology , Entamoeba histolytica/growth & development , Entamoeba histolytica/pathogenicity , Virulence Factors/genetics , Adult , Amino Acid Sequence , Animals , Cloning, Molecular , Colon/pathology , Cricetinae , Dysentery, Amebic/genetics , Entamoeba histolytica/genetics , Host-Parasite Interactions/genetics , Humans , Male , Mesocricetus , Models, Molecular , Molecular Sequence Data , Sequence Homology, Amino Acid , Virulence Factors/metabolism , beta-Amylase/genetics , beta-Amylase/metabolismABSTRACT
Alternative splicing and polyadenylation were observed pervasively in eukaryotic messenger RNAs. These alternative isoforms could either be consequences of physiological regulation or stochastic noise of RNA processing. To quantify the extent of stochastic noise in splicing and polyadenylation, we analyzed the alternative usage of splicing and polyadenylation sites in Entamoeba histolytica using RNA-Seq. First, we identified a large number of rarely spliced alternative junctions and then showed that the occurrence of these alternative splicing events is correlated with splicing site sequence, occurrence of constitutive splicing events and messenger RNA abundance. Our results implied the majority of these alternative splicing events are likely to be stochastic error of splicing machineries, and we estimated the corresponding error rates. Second, we observed extensive microheterogeneity of polyadenylation cleavage sites, and the extent of such microheterogeneity is correlated with the occurrence of constitutive cleavage events, suggesting most of such microheterogeneity is likely to be stochastic. Overall, we only observed a small fraction of alternative splicing and polyadenylation isoforms that are unlikely to be solely stochastic, implying the functional relevance of alternative splicing and polyadenylation in E. histolytica is limited. Lastly, we revised the gene models and annotated their 3'UTR in AmoebaDB, providing valuable resources to the community.
Subject(s)
Alternative Splicing , Entamoeba histolytica/genetics , Polyadenylation , Entamoeba histolytica/metabolism , Exons , Introns , Models, Genetic , Nucleotide Motifs , Poly A/analysis , RNA Isoforms/analysis , RNA, Messenger/chemistry , Stochastic ProcessesABSTRACT
Adaptation to nutritional changes is a key feature for successful survival of a pathogen within its host. The protozoan parasite Entamoeba histolytica normally colonizes the human colon and in rare occasions, this parasite spread to distant organs, such as the liver. E. histolytica obtains most of its energy from the fermentation of glucose into ethanol. In this study, we were intrigued to know how this parasite reacts to changes in glucose availability and we addressed this issue by performing a DNA microarray analysis of gene expression. Results show that parasites that were adapted to growth in absence of glucose increased their virulence and altered the transcription of several genes. One of these genes is the dihydropyrimidine dehydrogenase (DPD), which is involved in degradation of pyrimidines. We showed that this gene is crucial for the parasite's growth when the availability of glucose is limited. These data contribute to our understanding of the parasite's ability to survive in glucose-poor environments and reveal a new role for the DPD enzyme.
Subject(s)
Dihydrouracil Dehydrogenase (NADP)/metabolism , Entamoeba histolytica/enzymology , Entamoeba histolytica/physiology , Virulence Factors/metabolism , Dihydrouracil Dehydrogenase (NADP)/genetics , Energy Metabolism , Entamoeba histolytica/growth & development , Gene Expression Profiling , Glucose/metabolism , Pyrimidines/metabolism , Survival Analysis , Virulence Factors/geneticsABSTRACT
Introduction: Breast cancer (BC) is the leading cause of death among women, primarily due to its potential for metastasis. As BC progresses, the extracellular matrix (ECM) produces more type-I collagen, resulting in increased stiffness. This alteration influences cellular behaviors such as migration, invasion, and metastasis. Specifically, cancer cells undergo changes in gene expression that initially promote an epithelial-to-mesenchymal transition (EMT) and subsequently, a transition from a mesenchymal to an amoeboid (MAT) migration mode. In this way, cancer cells can migrate more easily through the stiffer microenvironment. Despite their importance, understanding MATs remains challenging due to the difficulty of replicating in vitro the conditions for cell migration that are observed in vivo. Methods: To address this challenge, we developed a three-dimensional (3D) growth system that replicates the different matrix properties observed during the progression of a breast tumor. We used this model to study the migration and invasion of the Triple-Negative BC (TNBC) cell line MDA-MB-231, which is particularly subject to metastasis. Results: Our results indicate that denser collagen matrices present a reduction in porosity, collagen fiber size, and collagen fiber orientation, which are associated with the transition of cells to a rounder morphology with bleb-like protrusions. We quantified how this transition is associated with a more persistent migration, an enhanced invasion capacity, and a reduced secretion of matrix metalloproteinases. Discussion: Our findings suggest that the proposed 3D growth conditions (especially those with high collagen concentrations) mimic key features of MATs, providing a new platform to study the physiology of migratory transitions and their role in BC progression.
ABSTRACT
The extracellular matrix (ECM) and its role in the outcome of infectious diseases have been poorly investigated. In this study, we determined the impact of the collagen fibres architecture on the invasive process of the enteric parasite Entamoeba histolytica. The behaviour of E. histolytica wild-type and silenced for the cysteine protease A5 (CP-A5) were compared on a three-dimensional collagen matrix and within human colon fragments for fibrillar collagen cleavage and migration. The interstitial collagen fibres within the connective tissue of the human colon, visualized by multiphoton and second harmonic generation signals imaging, presented a dense scaffold at the subepithelial level and a loose meshwork within the chorion. To penetrate the tissue, E. histolytica migrated on the dense scaffold that remained intact, reached the crypt of Lieberkhün, migrated along and then disorganized the loose scaffold to escape into the mucosa. Interestingly, in vitro, CP-A5 was not required for collagenase activity and migration through the matrix but was necessary within the tissue environment for collagen meshwork remodelling and subsequent invasion. The data point out that further step of invasion relay with ECM destruction that requires human components induced or activated in the presence of CP-A5.
Subject(s)
Colon/pathology , Colon/parasitology , Entamoeba histolytica/pathogenicity , Fibrillar Collagens/metabolism , Cell Movement , Connective Tissue/parasitology , Connective Tissue/pathology , Humans , Intestinal Mucosa/parasitology , Intestinal Mucosa/pathology , Microscopy, Fluorescence, MultiphotonABSTRACT
The amoeba parasite Entamoeba histolytica 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 E. histolytica 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 E. histolytica 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 E. histolytica is a resident of the complex intestinal ecosystem. The goal is to eradicate amoebiasis from the planet, but the parasitic life of E. histolytica is ancient and complex and will likely continue to evolve with humans. Advances in these topics are summarized here.
Subject(s)
Amebiasis , Entamoeba histolytica , Humans , Entamoeba histolytica/genetics , Virulence , Ecosystem , Amebiasis/parasitology , IntestinesABSTRACT
Amoebae found in aquatic and terrestrial environments encompass various pathogenic species, including the parasite Entamoeba histolytica and the free-living Acanthamoeba castellanii. Both microorganisms pose significant threats to public health, capable of inducing life-threatening effects on humans. These amoebae exist in two cellular forms: trophozoites and cysts. The trophozoite stage is the form used for growth and reproduction while the cyst stage is the resistant and disseminating form. Cysts occur after cellular metabolism slowdown due to nutritional deprivation or the appearance of environmental conditions unfavourable to the amoebae's growth and division. The initiation of encystation is accompanied by the activation of stress responses, and scarce data indicate that encystation shares factors and mechanisms identified in stress responses occurring in trophozoites exposed to toxic compounds derived from human immune defence. Although some "omics" analyses have explored how amoebae respond to diverse stresses, these studies remain limited and rarely report post-translational modifications that would provide knowledge on the molecular mechanisms underlying amoebae-specific stress responses. In this review, we discuss ubiquitin-like proteins associated with encystation and cell survival during oxidative damage. We aim to shed light on the signalling pathways involved in amoebic defence mechanisms, with a focus on their potential clinical implications against pathogenic amoebae, addressing the pressing need for effective therapies.