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Current Opinion in Chemical Biology Aug 2023Intracellular protozoan parasites are responsible for wide-spread infectious diseases. These unicellular pathogens have complex, multi-host life cycles, which present... (Review)
Review
Intracellular protozoan parasites are responsible for wide-spread infectious diseases. These unicellular pathogens have complex, multi-host life cycles, which present challenges for investigating their basic biology and for discovering vulnerabilities that could be exploited for disease control. Throughout development, parasite proteomes are dynamic and support stage-specific functions, but detection of these proteins is often technically challenging and complicated by the abundance of host proteins. Thus, to elucidate key parasite processes and host-pathogen interactions, labeling strategies are required to track pathogen proteins during infection. Herein, we discuss the application of bioorthogonal non-canonical amino acid tagging and proximity-dependent labeling to broadly study protozoan parasites and include outlooks for future applications to study Plasmodium, the causative agent of malaria. We highlight the potential of these technologies to provide spatiotemporal labeling with selective parasite protein enrichment, which could enable previously unattainable insight into the biology of elusive developmental stages.
Topics: Animals; Parasites; Proteome; Protozoan Proteins; Malaria; Life Cycle Stages
PubMed: 37192562
DOI: 10.1016/j.cbpa.2023.102316 -
Acta Tropica Jul 2023Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated... (Review)
Review
Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated proteins might express on both parasite structure and secretion and in parasite-infected host cells. In addition to the characterization of these pivotal proteins, describing their mechanism of action can be also fruitful in recognizing their roles in the pathogenesis of parasitic infections. Accordingly, this study presents the most prominent ANXs thus far identified and their relevant functions in parasites and infected host cells during pathogenesis, especially in the most important intracellular protozoan parasitic infections including leishmaniasis, toxoplasmosis, malaria and trypanosomiasis. The data provided in this study demonstrate that the helminth parasites most probably express and secret ANXs to develop pathogenesis while the modulation of the host-ANXs could be employed as a crucial strategy by intracellular protozoan parasites. Moreover, such data highlight that the use of analogs of both parasite and host ANX peptides (which mimic or regulate ANXs physiological functions through various strategies) might suggest novel therapeutic insights into the treatment of parasitic infections. Furthermore, due to the prominent immunoregulatory activities of ANXs during most parasitic infections and the expression levels of these proteins in some parasitic infected tissues, such multifunctional proteins might be also potentially relevant as vaccine and diagnostic biomarkers. We also suggest some prospects and insights that could be useful and applicable to form the basis of future experimental studies.
Topics: Animals; Humans; Annexins; Parasitic Diseases; Protozoan Infections; Malaria; Leishmaniasis; Parasites
PubMed: 37172709
DOI: 10.1016/j.actatropica.2023.106942 -
Trends in Parasitology Aug 2023To best understand parasite, host, and vector morphologies, host-parasite interactions, and to develop new drug and vaccine targets, structural data should, ideally, be... (Review)
Review
To best understand parasite, host, and vector morphologies, host-parasite interactions, and to develop new drug and vaccine targets, structural data should, ideally, be obtained and visualised in three dimensions (3D). Recently, there has been a significant uptake of available 3D volume microscopy techniques that allow collection of data across centimetre (cm) to Angstrom (Å) scales by utilising light, X-ray, electron, and ion sources. Here, we present and discuss microscopy tools available for the collection of 3D structural data, focussing on electron microscopy-based techniques. We highlight their strengths and limitations, such that parasitologists can identify techniques best suited to answer their research questions. Additionally, we review the importance of volume microscopy to the advancement of the field of parasitology.
Topics: Animals; Microscopy; Parasites; Host-Parasite Interactions
PubMed: 37302958
DOI: 10.1016/j.pt.2023.05.004 -
PloS One 2022Parasite species richness is influenced by a range of drivers including host related factors (e.g. host size) and environmental factors (e.g. seawater temperature)....
Parasite species richness is influenced by a range of drivers including host related factors (e.g. host size) and environmental factors (e.g. seawater temperature). However, identification of modulators of parasite species richness remains one of the great unanswered questions in ecology. The common cockle Cerastoderma edule is renowned for its diversity and abundance of parasites, yet drivers of parasite species richness in cockles have not been examined to investigate the association of both macro and microparasite communities. Using cockles as a model species, some of the key drivers of parasite prevalence and parasite species richness were investigated. Objectives of this 19-month survey were to determine the influence of the environment, host-parasite dynamics and parasite associations on parasite species richness and prevalence at two different geographic latitudes, chosen based on environmental differences. The highest parasite species richness was recorded in the northern sites, and this was potentially influenced by a range of interactions between the host, the pathogens and the environment. Parasite prevalence increased with host size and age, and parasite species richness increased with reduced salinity. A number of interactions between parasites, and between parasites and pathologies may be influencing parasite infection dynamics. New and concerning information is also presented regarding interactions between parasites and their environment. A number of parasites and potential pathogens (bacteria, Trichodina ciliates, metacercariae, trematode sporocysts) may be advantaged under climate change conditions (warming seas, increased precipitation), increasing disease incidence, which may prove detrimental not just for cockles, but for other bivalve species in the future.
Topics: Animals; Cardiidae; Host-Parasite Interactions; Parasites; Prevalence; Trematoda
PubMed: 36155981
DOI: 10.1371/journal.pone.0274474 -
Molecular and Biochemical Parasitology 2016Representatives of all major lineages of eukaryotes contain peroxisomes with similar morphology and mode of biogenesis, indicating a monophyletic origin of the... (Review)
Review
Representatives of all major lineages of eukaryotes contain peroxisomes with similar morphology and mode of biogenesis, indicating a monophyletic origin of the organelles within the common ancestor of all eukaryotes. Peroxisomes originated from the endoplasmic reticulum, but despite a common origin and shared morphological features, peroxisomes from different organisms show a remarkable diversity of enzyme content and the metabolic processes present can vary dependent on nutritional or developmental conditions. A common characteristic and probable evolutionary driver for the origin of the organelle is an involvement in lipid metabolism, notably HO-dependent fatty-acid oxidation. Subsequent evolution of the organelle in different lineages involved multiple acquisitions of metabolic processes-often involving retargeting enzymes from other cell compartments-and losses. Information about peroxisomes in protists is still scarce, but available evidence, including new bioinformatics data reported here, indicate striking diversity amongst free-living and parasitic protists from different phylogenetic supergroups. Peroxisomes in only some protists show major involvement in HO-dependent metabolism, as in peroxisomes of mammalian, plant and fungal cells. Compartmentalization of glycolytic and gluconeogenic enzymes inside peroxisomes is characteristic of kinetoplastids and diplonemids, where the organelles are hence called glycosomes, whereas several other excavate parasites (Giardia, Trichomonas) have lost peroxisomes. Amongst alveolates and amoebozoans patterns of peroxisome loss are more complicated. Often, a link is apparent between the niches occupied by the parasitic protists, nutrient availability, and the absence of the organelles or their presence with a specific enzymatic content. In trypanosomatids, essentiality of peroxisomes may be considered for use in anti-parasite drug discovery.
Topics: Animals; Biological Evolution; Energy Metabolism; Oxidation-Reduction; Parasites; Peroxisomes
PubMed: 26896770
DOI: 10.1016/j.molbiopara.2016.02.005 -
Molecular and Biochemical Parasitology Jul 2016Although it is regarded as self-evident that parasites interact with their hosts, with the primary aim of enhancing their own survival and transmission, the extent to... (Review)
Review
Although it is regarded as self-evident that parasites interact with their hosts, with the primary aim of enhancing their own survival and transmission, the extent to which unicellular parasites communicate with each has been severely underestimated. Recent publications show that information is commonly exchanged between parasites of the same species and that this can govern their decisions to divide, to differentiate or to migrate as a group. Communication can take the form of soluble secreted factors, extracellular vesicles or contact between cells. Extracellular parasites can do this directly, while intracellular parasites use the infected host cell - or components derived from it - as an intermediary. By emitting signals that can be dispersed within the host, parasites can also have long-distance effects on the course of an infection and its pathology. This article presents an overview of recent developments in this field and draws attention to some older work that merits re-examination.
Topics: Adaptation, Physiological; Animals; Cell Communication; Gene Expression Regulation; Parasites; Signal Transduction
PubMed: 27211242
DOI: 10.1016/j.molbiopara.2016.05.008 -
Frontiers in Cellular and Infection... 2020Extracellular vesicles (EVs) are membranous structures formed during biological processes in living organisms. For protozoan parasites, secretion of EVs can occur... (Review)
Review
Extracellular vesicles (EVs) are membranous structures formed during biological processes in living organisms. For protozoan parasites, secretion of EVs can occur directly from the parasite organellar compartments and through parasite-infected or antigen-stimulated host cells in response to and physiological stressors. These secreted EVs characteristically reflect the biochemical features of their parasitic origin and activating stimuli. Here, we review the species-specific morphology and integrity of parasitic protozoan EVs in concurrence with the origin, functions, and internalization process by recipient cells. The activating stimuli for the secretion of EVs in pathogenic protozoa are discoursed alongside their biomolecules and specific immune cell responses to protozoan parasite-derived EVs. We also present some insights on the intricate functions of EVs in the context of protozoan parasitism.
Topics: Animals; Exosomes; Extracellular Vesicles; Host-Parasite Interactions; Parasites; Protozoan Proteins
PubMed: 32923407
DOI: 10.3389/fcimb.2020.00371 -
Genes Feb 2024Ion channels serve many cellular functions including ion homeostasis, volume regulation, signaling, nutrient acquisition, and developmental progression. Although the... (Review)
Review
Ion channels serve many cellular functions including ion homeostasis, volume regulation, signaling, nutrient acquisition, and developmental progression. Although the complex life cycles of malaria parasites necessitate ion and solute flux across membranes, the whole-genome sequencing of the human pathogen revealed remarkably few orthologs of known ion channel genes. Contrasting with this, biochemical studies have implicated the channel-mediated flux of ions and nutritive solutes across several membranes in infected erythrocytes. Here, I review advances in the cellular and molecular biology of ion channels in malaria parasites. These studies have implicated novel parasite genes in the formation of at least two ion channels, with additional ion channels likely present in various membranes and parasite stages. Computational approaches that rely on homology to known channel genes from higher organisms will not be very helpful in identifying the molecular determinants of these activities. Given their unusual properties, novel molecular and structural features, and essential roles in pathogen survival and development, parasite channels should be promising targets for therapy development.
Topics: Animals; Humans; Parasites; Ion Channels; Plasmodium falciparum; Ions; Malaria
PubMed: 38540355
DOI: 10.3390/genes15030296 -
Frontiers in Cellular and Infection... 2023
Topics: Animals; Parasites; Multiomics; Proteomics
PubMed: 37780851
DOI: 10.3389/fcimb.2023.1281638 -
European Journal of Pharmacology Sep 2014Ca(2+)-signaling pathways and intracellular Ca(2+) channels are present in protozoa. Ancient origin of inositol 1,4,5-trisphosphate receptors (IP3Rs) and other... (Review)
Review
Ca(2+)-signaling pathways and intracellular Ca(2+) channels are present in protozoa. Ancient origin of inositol 1,4,5-trisphosphate receptors (IP3Rs) and other intracellular channels predates the divergence of animals and fungi as evidenced by their presence in the choanoflagellate Monosiga brevicollis, the closest known relative to metazoans. The first protozoan IP3R cloned, from the ciliate Paramecium, displays strong sequence similarity to the rat type 3 IP3R. This ciliate has a large number of IP3- and ryanodine(Ry)-like receptors in six subfamilies suggesting the evolutionary adaptation to local requirements for an expanding diversification of vesicle trafficking. IP3Rs have also been functionally characterized in trypanosomatids, where they are essential for growth, differentiation, and establishment of infection. The presence of the mitochondrial calcium uniporter (MCU) in a number of protozoa indicates that mitochondrial regulation of Ca(2+) signaling is also an early appearance in evolution, and contributed to the discovery of the molecular nature of this channel in mammalian cells. There is only sequence evidence for the occurrence of two-pore channels (TPCs), transient receptor potential Ca(2+) channels (TRPCs) and intracellular mechanosensitive Ca(2+)-channels in Paramecium and in parasitic protozoa.
Topics: Animals; Calcium Channels; Ciliophora; Intracellular Space; Parasites; Protozoan Proteins
PubMed: 24291099
DOI: 10.1016/j.ejphar.2013.11.015