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Parasites & Vectors Nov 2020Toxoplasma gondii is a protozoan parasite that is the causative agent of toxoplasmosis, an infection with high prevalence worldwide. Most of the infected individuals are... (Review)
Review
Toxoplasma gondii is a protozoan parasite that is the causative agent of toxoplasmosis, an infection with high prevalence worldwide. Most of the infected individuals are either asymptomatic or have mild symptoms, but T. gondii can cause severe neurologic damage and even death of the fetus when acquired during pregnancy. It is also a serious condition in immunodeficient patients. The life-cycle of T. gondii is complex, with more than one infective form and several transmission pathways. In two animated videos, we describe the main aspects of this cycle, raising questions about poorly or unknown issues of T. gondii biology. Original plates, based on electron microscope observations, are also available for teachers, students and researchers. The main goal of this review is to provide a source of learning on the fundamental aspects of T. gondii biology to students and teachers contributing for better knowledge and control on this important parasite, and unique cell model. In addition, drawings and videos point to still unclear aspects of T. gondii lytic cycle that may stimulate further studies.
Topics: Animals; Female; Humans; Life Cycle Stages; Pregnancy; Prevalence; Toxoplasma; Toxoplasmosis; Video Recording
PubMed: 33228743
DOI: 10.1186/s13071-020-04445-z -
Parasites & Vectors Jan 2021Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. The asexual part of its life cycle can be perpetually sustained in a... (Review)
Review
Toxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. The asexual part of its life cycle can be perpetually sustained in a variety of intermediate hosts through a combination of carnivory and vertical transmission. However, T. gondii produces gametes only in felids after the predation of infected intermediate hosts. The parasite changes the behavior of its intermediate hosts by reducing their innate fear to cat odors and thereby plausibly increasing the probability that the definitive host will devour the infected host. Here, we provide a short description of such parasitic behavioral manipulation in laboratory rodents infected with T. gondii, along with a bird's eye view of underpinning biological changes in the host. We also summarize critical gaps and opportunities for future research in this exciting research area with broad implications in the transdisciplinary study of host-parasite relationships.
Topics: Animals; Behavior, Animal; Cats; Fear; Host-Parasite Interactions; Humans; Life Cycle Stages; Odorants; Rodentia; Toxoplasma; Toxoplasmosis, Animal
PubMed: 33494777
DOI: 10.1186/s13071-020-04528-x -
Clinical Microbiology Reviews Sep 2019Protozoan parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria... (Review)
Review
Protozoan parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild or severe symptoms, or fatal, depending on many factors such as parasite virulence and host immune status. Malaria can be treated with various drugs, with artemisinin-based combination therapies (ACTs) being the first-line choice. Recent advances in genetics and genomics of malaria parasites have contributed greatly to our understanding of parasite population dynamics, transmission, drug responses, and pathogenesis. However, knowledge gaps in parasite biology and host-parasite interactions still remain. Parasites resistant to multiple antimalarial drugs have emerged, while advanced clinical trials have shown partial efficacy for one available vaccine. Here we discuss genetic and genomic studies of biology, host-parasite interactions, population structures, mosquito infectivity, antigenic variation, and targets for treatment and immunization. Knowledge from these studies will advance our understanding of malaria pathogenesis, epidemiology, and evolution and will support work to discover and develop new medicines and vaccines.
Topics: Antimalarials; Drug Resistance; Evolution, Molecular; Genome, Protozoan; Humans; Malaria; Plasmodium
PubMed: 31366610
DOI: 10.1128/CMR.00019-19 -
Cell Host & Microbe Nov 2020Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These...
Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These adaptations drive their recognition, nondestructive penetration, and elaborate reengineering of the host's cells to promote their growth, dissemination, and the countering of host defenses. The evolution of unique apicomplexan cellular compartments is concomitant with vast proteomic novelty. Consequently, half of apicomplexan proteins are unique and uncharacterized. Here, we determine the steady-state subcellular location of thousands of proteins simultaneously within the globally prevalent apicomplexan parasite Toxoplasma gondii. This provides unprecedented comprehensive molecular definition of these unicellular eukaryotes and their specialized compartments, and these data reveal the spatial organizations of protein expression and function, adaptation to hosts, and the underlying evolutionary trajectories of these pathogens.
Topics: Apicomplexa; Biological Evolution; Epitopes; Host-Pathogen Interactions; Humans; Proteome; Proteomics; Protozoan Proteins; Toxoplasma
PubMed: 33053376
DOI: 10.1016/j.chom.2020.09.011 -
The Journal of Eukaryotic Microbiology Nov 2022Toxoplasma gondii belongs to the phylum Apicomplexa and is an important cause of congenital disease and infection in immunocompromised patients. T. gondii shares... (Review)
Review
Toxoplasma gondii belongs to the phylum Apicomplexa and is an important cause of congenital disease and infection in immunocompromised patients. T. gondii shares several characteristics with plants including a nonphotosynthetic plastid termed apicoplast and a multivesicular organelle that was named the plant-like vacuole (PLV) or vacuolar compartment (VAC). The name plant-like vacuole was selected based on its resemblance in composition and function to plant vacuoles. The name VAC represents its general vacuolar characteristics. We will refer to the organelle as PLVAC in this review. New findings in recent years have revealed that the PLVAC represents the lysosomal compartment of T. gondii which has adapted peculiarities to fulfill specific Toxoplasma needs. In this review, we discuss the composition and functions of the PLVAC highlighting its roles in ion storage and homeostasis, endocytosis, exocytosis, and autophagy.
Topics: Humans; Toxoplasma; Vacuoles; Protozoan Proteins; Apicoplasts; Plants
PubMed: 36218001
DOI: 10.1111/jeu.12951 -
Cell Host & Microbe Apr 2023Cryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades and extensively...
Cryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades and extensively remodels intestinal epithelial cells, building an elaborate interface structure. How this occurs at the molecular level and the contributing parasite factors are largely unknown. Here, we generated a whole-cell spatial proteome of the Cryptosporidium sporozoite and used genetic and cell biological experimentation to discover the Cryptosporidium-secreted effector proteome. These findings reveal multiple organelles, including an original secretory organelle, and generate numerous compartment markers by tagging native gene loci. We show that secreted proteins are delivered to the parasite-host interface, where they assemble into different structures including a ring that anchors the parasite into its unique epicellular niche. Cryptosporidium thus uses a complex set of secretion systems during and following invasion that act in concert to subjugate its host cell.
Topics: Child, Preschool; Child; Humans; Cryptosporidium; Proteome; Cryptosporidiosis; Organelles; Cryptosporidium parvum; Protozoan Proteins; Host-Parasite Interactions
PubMed: 36958336
DOI: 10.1016/j.chom.2023.03.001 -
Parasites & Vectors Jan 2022Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are... (Review)
Review
Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are intrinsically modulated during developmental transitions, physiological processes and disease progression. Also, proteins are integral components of parasite structural elements and organelles. Among apicomplexan parasites, Eimeria species are an important disease aetiology for economically important animals wherein identification and characterisation of proteins have been long-winded. Nonetheless, this review seeks to give a comprehensive overview of constitutively expressed Eimeria proteins. These molecules are discussed across developmental stages, organelles and sub-cellular components vis-à-vis their biological functions. In addition, hindsight and suggestions are offered with intention to summarise the existing trend of eimerian protein characterisation and to provide a baseline for future studies.
Topics: Animals; Antigens, Protozoan; Apicomplexa; Bodily Secretions; Chickens; Coccidiosis; Eimeria; Eimeria tenella; Genes, Protozoan; Host-Parasite Interactions; Humans; Membrane Proteins; Merozoites; Oocysts; Organelles; Peptide Hydrolases; Poultry Diseases; Protein Transport; Sporozoites
PubMed: 35073987
DOI: 10.1186/s13071-022-05159-0 -
Proceedings of the National Academy of... Oct 2020Asymptomatic carriers of parasites hamper malaria control and eradication. Achieving malaria eradication requires ultrasensitive diagnostics for low parasite density...
Asymptomatic carriers of parasites hamper malaria control and eradication. Achieving malaria eradication requires ultrasensitive diagnostics for low parasite density infections (<100 parasites per microliter blood) that work in resource-limited settings (RLS). Sensitive point-of-care diagnostics are also lacking for nonfalciparum malaria, which is characterized by lower density infections and may require additional therapy for radical cure. Molecular methods, such as PCR, have high sensitivity and specificity, but remain high-complexity technologies impractical for RLS. Here we describe a CRISPR-based diagnostic for ultrasensitive detection and differentiation of , , , and , using the nucleic acid detection platform SHERLOCK (specific high-sensitivity enzymatic reporter unlocking). We present a streamlined, field-applicable, diagnostic comprised of a 10-min SHERLOCK parasite rapid extraction protocol, followed by SHERLOCK for 60 min for species-specific detection via fluorescent or lateral flow strip readout. We optimized one-pot, lyophilized, isothermal assays with a simplified sample preparation method independent of nucleic acid extraction, and showed that these assays are capable of detection below two parasites per microliter blood, a limit of detection suggested by the World Health Organization. Our and assays exhibited 100% sensitivity and specificity on clinical samples (5 and 10 samples). This work establishes a field-applicable diagnostic for ultrasensitive detection of asymptomatic carriers as well as a rapid point-of-care clinical diagnostic for nonfalciparum malaria species and low parasite density infections.
Topics: Carrier State; Clustered Regularly Interspaced Short Palindromic Repeats; Diagnostic Techniques and Procedures; Genetic Techniques; Humans; Malaria; Plasmodium
PubMed: 32958655
DOI: 10.1073/pnas.2010196117 -
The FEBS Journal Jan 2021The Apicomplexa phylum groups important human and animal pathogens that cause severe diseases, encompassing malaria, toxoplasmosis, and cryptosporidiosis. In common with... (Review)
Review
The Apicomplexa phylum groups important human and animal pathogens that cause severe diseases, encompassing malaria, toxoplasmosis, and cryptosporidiosis. In common with most organisms, apicomplexans rely on heme as cofactor for several enzymes, including cytochromes of the electron transport chain. This heme derives from de novo synthesis and/or the development of uptake mechanisms to scavenge heme from their host. Recent studies have revealed that heme synthesis is essential for Toxoplasma gondii tachyzoites, as well as for the mosquito and liver stages of Plasmodium spp. In contrast, the erythrocytic stages of the malaria parasites rely on scavenging heme from the host red blood cell. The unusual heme synthesis pathway in Apicomplexa spans three cellular compartments and comprises enzymes of distinct ancestral origin, providing promising drug targets. Remarkably given the requirement for heme, T. gondii can tolerate the loss of several heme synthesis enzymes at a high fitness cost, while the ferrochelatase is essential for survival. These findings indicate that T. gondii is capable of salvaging heme precursors from its host. Furthermore, heme is implicated in the activation of the key antimalarial drug artemisinin. Recent findings established that a reduction in heme availability corresponds to decreased sensitivity to artemisinin in T. gondii and Plasmodium falciparum, providing insights into the possible development of combination therapies to tackle apicomplexan parasites. This review describes the microeconomics of heme in Apicomplexa, from supply, either from de novo synthesis or scavenging, to demand by metabolic pathways, including the electron transport chain.
Topics: Animals; Anti-Infective Agents; Artemisinins; Cryptosporidium; Cytochromes; Erythrocytes; Ferrochelatase; Gene Expression; Heme; Host-Pathogen Interactions; Humans; Life Cycle Stages; Metabolic Networks and Pathways; Plasmodium berghei; Plasmodium falciparum; Protozoan Proteins; Toxoplasma
PubMed: 32530125
DOI: 10.1111/febs.15445 -
Trends in Parasitology Sep 2019Gregarine apicomplexans are closely related to parasites such as Plasmodium, Toxoplasma, and Cryptosporidium, which are causing severe health and economic burdens.... (Review)
Review
Gregarine apicomplexans are closely related to parasites such as Plasmodium, Toxoplasma, and Cryptosporidium, which are causing severe health and economic burdens. Colonizing only invertebrates and having no obvious medical relevance, they are mostly ignored in 'omics' studies, although gregarines are the most basal apicomplexans and therefore key players in the understanding of the evolution of parasitism in the Apicomplexa from free-living ancestors. They belong to the largest exclusively parasitic phylum, but is this perception actually true? The effects of gregarines on their hosts seem to cover the whole spectrum of symbiosis from mutualistic to parasitic. We suggest future research directions to understand the evolutionary role of gregarines, by elucidating their biology and interaction with their hosts and the hosts' microbiota.
Topics: Animals; Apicomplexa; Biological Evolution; Invertebrates; Symbiosis
PubMed: 31345767
DOI: 10.1016/j.pt.2019.06.013