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Experimental Parasitology Apr 2018Naegleria fowleri is a pathogenic amoeboflagellate most prominently known for its role as the etiological agent of the Primary Amoebic Meningoencephalitis (PAM), a... (Review)
Review
Naegleria fowleri is a pathogenic amoeboflagellate most prominently known for its role as the etiological agent of the Primary Amoebic Meningoencephalitis (PAM), a disease that afflicts the central nervous system and is fatal in more than 95% of the reported cases. Although being fatal and with potential risks for an increase in the occurrence of the pathogen in populated areas, the organism receives little public health attention. A great underestimation in the number of PAM cases reported is assumed, taking into account the difficulty in obtaining an accurate diagnosis. In this review, we summarize different techniques and methods used in the identification of the protozoan in clinical and environmental samples. Since it remains unclear whether the protozoan infection can be successfully treated with the currently available drugs, we proceed to discuss the current PAM therapeutic strategies and its effectiveness. Finally, novel compounds for potential treatments are discussed as well as research on vaccine development against PAM.
Topics: Antiprotozoal Agents; Central Nervous System Protozoal Infections; Drinking Water; Humans; Naegleria fowleri; Risk Factors; Vaccination
PubMed: 29501696
DOI: 10.1016/j.exppara.2018.02.010 -
How colonization bottlenecks, tissue niches, and transmission strategies shape protozoan infections.Trends in Parasitology Dec 2023Protozoan pathogens such as Plasmodium spp., Leishmania spp., Toxoplasma gondii, and Trypanosoma spp. are often associated with high-mortality, acute and chronic... (Review)
Review
Protozoan pathogens such as Plasmodium spp., Leishmania spp., Toxoplasma gondii, and Trypanosoma spp. are often associated with high-mortality, acute and chronic diseases of global health concern. For transmission and immune evasion, protozoans have evolved diverse strategies to interact with a range of host tissue environments. These interactions are linked to disease pathology, yet our understanding of the association between parasite colonization and host homeostatic disruption is limited. Recently developed techniques for cellular barcoding have the potential to uncover the biology regulating parasite transmission, dissemination, and the stability of infection. Understanding bottlenecks to infection and the in vivo tissue niches that facilitate chronic infection and spread has the potential to reveal new aspects of parasite biology.
Topics: Animals; Humans; Host-Parasite Interactions; Protozoan Infections; Parasites; Toxoplasma; Plasmodium
PubMed: 37839913
DOI: 10.1016/j.pt.2023.09.017 -
Molecular Immunology Apr 2021The trypanosomatid pathogens Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei, currently grouped as TriTryps, have evolved through the time to overcome the... (Review)
Review
The trypanosomatid pathogens Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei, currently grouped as TriTryps, have evolved through the time to overcome the upfront innate immune response and establish the infection in humans adapting many aspects of the parasite-cell host interaction. Extracellular vesicles (EVs) emerge as critical structures carrying different key molecules from parasites and target cells that interact continuously during infection. Current information regarding the structure and composition of these vesicles provide new insights into the primary role of TriTryps-EVs reviewed in this work. Expanding knowledge about these critical vesicular structures will promote advances in basic sciences and in translational applications controlling pathogenesis in the neglected tropical diseases caused by TriTryps.
Topics: Animals; Extracellular Vesicles; Host-Parasite Interactions; Humans; Immunity, Innate; Leishmania major; Protozoan Infections; Trypanosoma brucei brucei; Trypanosoma cruzi
PubMed: 33601226
DOI: 10.1016/j.molimm.2021.01.008 -
Trends in Parasitology Dec 2016The protein translation machineries of the apicoplast and mitochondrion-the two actively translating organelles of apicomplexan parasites-have potential sites for drug... (Review)
Review
The protein translation machineries of the apicoplast and mitochondrion-the two actively translating organelles of apicomplexan parasites-have potential sites for drug intervention against diseases caused by these organisms. Work in the past few years, particularly on Plasmodium falciparum and Toxoplasma gondii, has shown that a reduced machinery of enzymes and factors is sufficient for organellar translation, which is also supported by components shared with the cytosolic translation system. This interplay between eukaryotic and prokaryotic-like components for mRNA translation in organelles is reviewed here. We also discuss functional and structural aspects of factors mediating initiation, elongation, and termination of polypeptides, and recycling of the reduced ribosomes of the apicoplast and mitochondrion.
Topics: Animals; Apicomplexa; Apicoplasts; Drug Delivery Systems; Humans; Mitochondria; Protein Biosynthesis; Protozoan Infections; RNA, Protozoan
PubMed: 27527393
DOI: 10.1016/j.pt.2016.07.005 -
Expert Opinion on Therapeutic Targets Nov 2019: The proteasome is a multi-subunit enzyme complex responsible for the turnover of short-lived, abnormal or damaged proteins in eukaryotic cells. As organisms that... (Review)
Review
: The proteasome is a multi-subunit enzyme complex responsible for the turnover of short-lived, abnormal or damaged proteins in eukaryotic cells. As organisms that undergo rapid growth and cell division, protozoan parasites exist on the knife-edge of proteotoxic catastrophe and thus rely heavily on their protein quality control machinery for survival. Because of this, the proteasome has recently emerged as a desirable drug target.: This review focuses on efforts to identify protozoan parasite-specific proteasome inhibitors using substrate profiling, library screening, and evolution of resistance approaches to inform medicinal chemistry. Targeting the parasite's 20S proteasome chymotrypsin-like (β5) activity and selectively inhibiting protein turnover in parasites compared to human cells are critical properties of potent, selective inhibitors.: Proteasome inhibitors have the potential for rapid action against all stages, all species and all strains of plasmodium and kinetoplastid parasites. Given the high level of conservation of proteasome active sites in eukaryotes, an important challenge is achieving inhibitors that show sufficient selectivity while maintaining properties consistent with drug development.
Topics: Animals; Antiprotozoal Agents; Drug Development; Humans; Parasites; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Protozoan Infections
PubMed: 31679410
DOI: 10.1080/14728222.2019.1685981 -
European Journal of Clinical... Sep 2014Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that presents a protean spectrum of clinical manifestations, and may affect any organ. The typical... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that presents a protean spectrum of clinical manifestations, and may affect any organ. The typical course of SLE is insidious, slow, and progressive, with potential exacerbations and remissions, and even dramatically acute and rapidly fatal outcomes. Recently, infections have been shown to be highly associated with the onset and/or exacerbations of SLE, and their possible causative and/or protective role has been largely emphasized in the medical literature. However, the etiopathogenesis of SLE is still obscure and far from being completely elucidated. Among infections, particularly Epstein-Barr virus (EBV), parvovirus B19, retrovirus, and cytomegalovirus (CMV) infections might play a pivotal pathogenetic role. The multifaceted interactions between infections and autoimmunity reveal many possibilities for either causative or protective associations. Indeed, some infections, primarily protozoan infections, might confer protection from autoimmune processes, depending on the unique interaction between the microorganism and host. Further studies are needed in order to demonstrate that infectious agents might, indeed, be causative of SLE, and to address the potential clinical sequelae of infections in the field of autoimmunity.
Topics: Animals; Humans; Lupus Erythematosus, Systemic; Protozoan Infections; Virus Diseases
PubMed: 24715155
DOI: 10.1007/s10096-014-2098-7 -
Journal of Veterinary Pharmacology and... Apr 2018Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated... (Review)
Review
Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.
Topics: Acetonitriles; Animals; Antiprotozoal Agents; Coccidiosis; Encephalomyelitis, Equine; Horses; Nitriles; Protozoan Infections, Animal; Toxoplasmosis, Animal; Triazines
PubMed: 28833212
DOI: 10.1111/jvp.12450 -
Frontiers in Cellular and Infection... 2017The next-generation gene editing based on CRISPR (clustered regularly interspaced short palindromic repeats) has been successfully implemented in a wide range of... (Review)
Review
The next-generation gene editing based on CRISPR (clustered regularly interspaced short palindromic repeats) has been successfully implemented in a wide range of organisms including some protozoan parasites. However, application of such a versatile game-changing technology in molecular parasitology remains fairly underexplored. Here, we briefly introduce in human and mouse research and usher new directions to drive the parasitology research in the years to come. In precise, we outline contemporary ways to embolden existing apicomplexan and kinetoplastid parasite models by commissioning front-line gene-tailoring methods, and illustrate how we can break the enduring gridlock of gene manipulation in non-model parasitic protists to tackle intriguing questions that remain long unresolved otherwise. We show how a judicious solicitation of the CRISPR technology can eventually balance out the two facets of pathogen-host interplay.
Topics: Animals; Apicomplexa; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Editing; Humans; Kinetoplastida; Phylogeny; Protozoan Infections
PubMed: 28730142
DOI: 10.3389/fcimb.2017.00292 -
Neurology(R) Neuroimmunology &... Nov 2019Human African trypanosomiasis (HAT) is caused by infection due to protozoan parasites of the genus and is a major fatal disease throughout sub-Saharan Africa. After an... (Review)
Review
Human African trypanosomiasis (HAT) is caused by infection due to protozoan parasites of the genus and is a major fatal disease throughout sub-Saharan Africa. After an early hemolymphatic stage in which the peripheral tissues are infected, the parasites enter the CNS causing a constellation of neurologic features. Although the CNS stage of HAT has been recognized for over a century, the mechanisms generating the neuroinflammatory response are complex and not well understood. Therefore a better understanding of the mechanisms utilized by the parasites to gain access to the CNS compartment is critical to explaining the generation of neuroinflammation. Contrast-enhanced MRI in a murine model of HAT has shown an early and progressive deterioration of blood-CNS barrier function after trypanosome infection that can be reversed following curative treatment. However, further studies are required to clarify the molecules involved in this process. Another important determinant of brain inflammation is the delicate balance of proinflammatory and counterinflammatory mediators. In mouse models of HAT, proinflammatory mediators such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and CXCL10 have been shown to be crucial to parasite CNS invasion while administration of interleukin (IL)-10, a counter inflammatory molecule, reduces the CNS parasite burden as well as the severity of the neuroinflammatory response and the clinical symptoms associated with the infection. This review focuses on information, gained from both infected human samples and animal models of HAT, with an emphasis on parasite CNS invasion and the development of neuroinflammation.
Topics: Animals; Central Nervous System Protozoal Infections; Disease Models, Animal; Humans; Inflammation; Mice; Trypanosomiasis, African
PubMed: 31467039
DOI: 10.1212/NXI.0000000000000610 -
Biological Reviews of the Cambridge... Apr 2020Involvement of the central nervous system (CNS) is the most severe consequence of some parasitic infections. Protozoal infections comprise a group of diseases that... (Review)
Review
Involvement of the central nervous system (CNS) is the most severe consequence of some parasitic infections. Protozoal infections comprise a group of diseases that together affect billions of people worldwide and, according to the World Health Organization, are responsible for more than 500000 deaths annually. They include African and American trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, and amoebiasis. Mechanisms underlying invasion of the brain parenchyma by protozoa are not well understood and may depend on parasite nature: a vascular invasion route is most common. Immunosuppression favors parasite invasion into the CNS and therefore the host immune response plays a pivotal role in the development of a neuropathology in these infectious diseases. In the brain, microglia are the resident immune cells active in defense against pathogens that target the CNS. Beside their direct role in innate immunity, they also play a principal role in coordinating the trafficking and recruitment of other immune cells from the periphery to the CNS. Despite their evident involvement in the neuropathology of protozoan infections, little attention has given to microglia-parasite interactions. This review describes the most prominent features of microglial cells and protozoan parasites and summarizes the most recent information regarding the reaction of microglial cells to parasitic infections. We highlight the involvement of the periphery-brain axis and emphasize possible scenarios for microglia-parasite interactions.
Topics: Central Nervous System Protozoal Infections; Eukaryota; Humans; Microglia
PubMed: 31682077
DOI: 10.1111/brv.12566