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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 -
International Journal of Molecular... Jul 2023This review of human amoebiasis is based on the most current knowledge of pathogenesis, diagnosis, treatment, and Entamoeba/microbiota interactions. The most relevant... (Review)
Review
This review of human amoebiasis is based on the most current knowledge of pathogenesis, diagnosis, treatment, and Entamoeba/microbiota interactions. The most relevant findings during this last decade about the parasite and the disease are related to the possibility of culturing trophozoites of different isolates from infected individuals that allowed the characterization of the multiple pathogenic mechanisms of the parasite and the understanding of the host-parasite relationship in the human. Second, the considerable advances in molecular biology and genetics help us to analyze the genome of , their genetic diversity, and the association of specific genotypes with the different amoebic forms of human amoebiasis. Based on this knowledge, culture and/or molecular diagnostic strategies are now available to determine the species and genotype responsible for invasive intestinal or extraintestinal amoebiasis cases. Likewise, the extensive knowledge of the immune response in amoebiasis with the appearance of new technologies made it possible to design diagnostic tools now available worldwide. Finally, the understanding of the interaction between the species and the intestinal microbiota aids the understanding of the ecology of this parasite in the human environment. These relevant findings will be discussed in this review.
Topics: Humans; Entamoeba histolytica; Ecosystem; Amebiasis; Dysentery, Amebic; Intestines; Entamoeba
PubMed: 37511519
DOI: 10.3390/ijms241411755 -
The Journal of Cell Biology Sep 2023Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key...
Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key roles in many endocytic pathways including phagocytosis and macropinocytosis. PI(3,5)P2 is generated by the phosphoinositide 5-kinase PIKfyve, which is critical for phagosomal digestion and antimicrobial activity. However PI(3,5)P2 dynamics and regulation remain unclear due to lack of reliable reporters. Using the amoeba Dictyostelium discoideum, we identify SnxA as a highly selective PI(3,5)P2-binding protein and characterize its use as a reporter for PI(3,5)P2 in both Dictyostelium and mammalian cells. Using GFP-SnxA, we demonstrate that Dictyostelium phagosomes and macropinosomes accumulate PI(3,5)P2 3 min after engulfment but are then retained differently, indicating pathway-specific regulation. We further find that PIKfyve recruitment and activity are separable and that PIKfyve activation stimulates its own dissociation. SnxA is therefore a new tool for reporting PI(3,5)P2 in live cells that reveals key mechanistic details of the role and regulation of PIKfyve/PI(3,5)P2.
Topics: Animals; Dictyostelium; Endosomes; Mammals; Phagosomes; Phosphatidylinositols; Phosphatidylinositol 3-Kinases
PubMed: 37382666
DOI: 10.1083/jcb.202209077 -
Parasitology Research Dec 2023The members of genus Acanthamoeba are the etiological agent of uncommon but severe or even fatal opportunistic infections in human beings. The presence of different... (Review)
Review
The members of genus Acanthamoeba are the etiological agent of uncommon but severe or even fatal opportunistic infections in human beings. The presence of different classes of intracellular and extracellular proteases including serine proteases, cysteine proteases, and metalloproteases has been well documented in environmental and clinical isolates of Acanthamoeba spp. However, the role of the proteolytic enzymes in physiological, biological, and pathological mechanisms of the amoeba remains partially investigated. Some attempts have been conducted using various methods to determine the profile of proteases (number, class, optimal conditions, and activity of the enzymes), and possible pathogenicity mechanism of the proteolytic enzymes (various protein substrate degradation, cytopathic effect on different cell lines). In some cases, it was attempted to correlate intracellular and extracellular protease profile with pathogenicity potential of strains. This review revealed that the protease profile of different strains of Acanthamoeba was extremely complex, therefore, further comprehensive studies with application of a combination of various methods may help to elucidate the role of the enzymes.
Topics: Humans; Acanthamoeba; Serine Proteases; Serine Endopeptidases; Acanthamoeba Keratitis; Cell Line
PubMed: 38063887
DOI: 10.1007/s00436-023-08059-z -
Diagnostic Microbiology and Infectious... Aug 2023The diversity of microbiota is different in each person. Many health problems such as autoimmune diseases, diabetes, cardiovascular diseases, and depression can be... (Review)
Review
The diversity of microbiota is different in each person. Many health problems such as autoimmune diseases, diabetes, cardiovascular diseases, and depression can be caused by microbiota imbalance. Since the parasite needs a host to survive, it interacts closely with the microbiota elements. Blastocystis acts on the inflammatory state of the intestine and may cause various gastrointestinal symptoms, on the contrary, it is more important for gut health because it causes bacterial diversity and richness. Blastocystis is associated with changes in gut microbiota composition, the ultimate indicator of which is the Firmicutes/Bacteroidetes ratio. The Bifidobacterium genus was significantly reduced in IBS patients and Blastocystis, and there is a significant decrease in Faecalibacterium prausnitzii, which has anti-inflammatory properties in Blastocystis infection without IBS. Lactobacillus species reduce the presence of Giardia, and the produced bacteriocins prevent parasite adhesion. The presence of helminths has been strongly associated with the transition from Bacteroidetes to Firmicutes and Clostridia. Contrary to Ascaris, alpha diversity in the intestinal microbiota decreases in chronic Trichuris muris infection, and growth and nutrient metabolism efficiency can be suppressed. Helminth infections indirectly affect mood and behavior in children through their effects on microbiota change. The main and focus of this review is to address the relationship of parasites with microbiota elements and to review the data about what changes they cause. Microbiota studies have gained importance recently and it is thought that it will contribute to the treatment of many diseases as well as in the fight against parasitic diseases in the future.
Topics: Animals; Humans; Bacteroidetes; Blastocystis; Blastocystis Infections; Feces; Firmicutes; Gastrointestinal Microbiome; Irritable Bowel Syndrome; Microbiota; Parasites
PubMed: 37267741
DOI: 10.1016/j.diagmicrobio.2023.115954 -
Laboratory Medicine Sep 2023Primary amebic meningoencephalitis (PAM) is a fulminant fatal human disease caused by the free-living amoeba Naegleria fowleri. Infection occurs after inhalation of... (Review)
Review
Primary amebic meningoencephalitis (PAM) is a fulminant fatal human disease caused by the free-living amoeba Naegleria fowleri. Infection occurs after inhalation of water containing the amoeba, typically after swimming in bodies of warm freshwater. N. fowleri migrates to the brain where it incites meningoencephalitis and cerebral edema leading to death of the patient 7 to 10 days postinfection. Although the disease is rare, it is almost always fatal and believed to be underreported. The incidence of PAM in countries other than the United States is unclear and possibly on track to being an emerging disease. Poor prognosis is caused by rapid progression, suboptimal treatment, and underdiagnosis. As diagnosis is often performed postmortem and testing is only performed by a few laboratories, more accessible testing is necessary. This article reviews the current methods used in the screening and confirmation of PAM and makes recommendations for improved diagnostic practices and awareness.
Topics: Humans; United States; Central Nervous System Protozoal Infections; Brain; Meningoencephalitis; Naegleria fowleri; Clinical Laboratory Techniques; Amebiasis
PubMed: 36638160
DOI: 10.1093/labmed/lmac158 -
Current Opinion in Cell Biology Dec 2023Lamins are nuclear intermediate filament proteins with important, well-established roles in humans and other vertebrates. Lamins interact with DNA and numerous proteins... (Review)
Review
Lamins are nuclear intermediate filament proteins with important, well-established roles in humans and other vertebrates. Lamins interact with DNA and numerous proteins at the nuclear envelope to determine the mechanical properties of the nucleus, coordinate chromatin organization, and modulate gene expression. Many of these functions are conserved in the lamin homologs found in basal metazoan organisms, including Drosophila and Caenorhabditis elegans. Lamin homologs have also been recently identified in non-metazoans, like the amoeba Dictyostelium discoideum, yet how these proteins compare functionally to the metazoan isoforms is only beginning to emerge. A better understanding of these distantly related lamins is not only valuable for a more complete picture of eukaryotic evolution, but may also provide new insights into the function of vertebrate lamins.
Topics: Humans; Animals; Lamins; Dictyostelium; Nuclear Envelope; Drosophila; Intermediate Filament Proteins; Caenorhabditis elegans; Nuclear Lamina
PubMed: 37871500
DOI: 10.1016/j.ceb.2023.102267 -
Turkiye Parazitolojii Dergisi Sep 2023is an anaerobic protozoan with global importance because of infecting a variety of hosts and having high prevalence in many countries. isolates display remarkable... (Review)
Review
is an anaerobic protozoan with global importance because of infecting a variety of hosts and having high prevalence in many countries. isolates display remarkable genetic differences, and many subtypes (STs) have currently been defined based on polymorphism in coding gene. Each 25 subtype may have different characteristics such as pathogenicity, host specificity, and structural variations. Most current research on has focused on these differences and molecular epidemiology. This review aimed to provide a summary of subtype distribution in Türkiye. Regarding human samples, 16 manuscripts were found in the literature, which presented 783 isolates from 9 cities in Türkiye. The most common subtype was ST3 (47.9%), the others were ST1 30 (17.5%), ST2 (14.7%), ST4 (4%), and ST5-ST7 (15.9%). There were few studies on animal hosts and environmental samples. The faecal samples from rats, farm, and pet animals were examined for subtypes and ST1, ST3, ST4-ST7, ST10, and ST12-ST14 were reported. In addition, two studies reported ST1 and ST3 subtypes in environmental water samples. In conclusion, the review of available literature showed that a systematic understanding of the subtype distribution of 35 in Türkiye is still lacking. Most of the studies were performed in a limited number of cities, animal hosts, and environmental samples, therefore, more studies from different provinces are needed in forthcoming research. The majority studies were performed in a limited number of provinces, animal species and very few environmental samples, so in the future; there is a need of novel studies that evaluate more samples from different provinces.
Topics: Humans; Animals; Rats; Blastocystis; Cities; Feces; Polymorphism, Genetic
PubMed: 37724369
DOI: 10.4274/tpd.galenos.2023.79188 -
FEBS Letters May 2024Perilipins are abundant lipid droplet (LD) proteins present in all metazoans and also in Amoebozoa and fungi. Humans express five perilipins, which share a similar... (Review)
Review
Perilipins are abundant lipid droplet (LD) proteins present in all metazoans and also in Amoebozoa and fungi. Humans express five perilipins, which share a similar domain organization: an amino-terminal PAT domain and an 11-mer repeat region, which can fold into amphipathic helices that interact with LDs, followed by a structured carboxy-terminal domain. Variations of this organization that arose during vertebrate evolution allow for functional specialization between perilipins in relation to the metabolic needs of different tissues. We discuss how different features of perilipins influence their interaction with LDs and their cellular targeting. PLIN1 and PLIN5 play a direct role in lipolysis by regulating the recruitment of lipases to LDs and LD interaction with mitochondria. Other perilipins, particularly PLIN2, appear to protect LDs from lipolysis, but the molecular mechanism is not clear. PLIN4 stands out with its long repetitive region, whereas PLIN3 is most widely expressed and is used as a nascent LD marker. Finally, we discuss the genetic variability in perilipins in connection with metabolic disease, prominent for PLIN1 and PLIN4, underlying the importance of understanding the molecular function of perilipins.
Topics: Humans; Lipid Droplets; Animals; Perilipins; Lipid Metabolism; Lipolysis; Perilipin-1
PubMed: 38140813
DOI: 10.1002/1873-3468.14792 -
Science Advances Oct 2023Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel...
Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and its immunosuppressive microenvironment. Using a panel of pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse models, and intravital imaging, we demonstrate that ROCK-Myosin II activity in PDAC cells supports a transcriptional program conferring amoeboid invasive and immunosuppressive traits and in vivo metastatic abilities. Moreover, we find that immune checkpoint CD73 is highly expressed in amoeboid PDAC cells and drives their invasive, metastatic, and immunomodulatory traits. Mechanistically, CD73 activates RhoA-ROCK-Myosin II downstream of PI3K. Tissue microarrays of human PDAC biopsies combined with bioinformatic analysis reveal that rounded-amoeboid invasive cells with high CD73-ROCK-Myosin II activity and their immunosuppressive microenvironment confer poor prognosis to patients. We propose targeting amoeboid PDAC cells as a therapeutic strategy.
Topics: Animals; Humans; Mice; Adenocarcinoma; Amoeba; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cell Movement; Cytoskeletal Proteins; Immunosuppression Therapy; Myosin Type II; Pancreatic Neoplasms; Tumor Microenvironment
PubMed: 37851808
DOI: 10.1126/sciadv.adi0244