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Nature Jan 2024The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5...
The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5 (refs. ), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies or nanobodies against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies, binds to the PfCSS-PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design.
Topics: Animals; Humans; Antibodies, Neutralizing; Antigens, Protozoan; Cryoelectron Microscopy; Disulfides; Erythrocytes; Malaria Vaccines; Malaria, Falciparum; Merozoites; Multiprotein Complexes; Parasites; Plasmodium falciparum; Protozoan Proteins
PubMed: 38123677
DOI: 10.1038/s41586-023-06856-1 -
PLoS Computational Biology Feb 2022Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology of these organisms is limited by economic and experimental...
Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology of these organisms is limited by economic and experimental constraints. Accordingly, studies of one parasite are frequently extrapolated to infer knowledge about another parasite, across and within genera. Model in vitro or in vivo systems are frequently used to enhance experimental manipulability, but these systems generally use species related to, yet distinct from, the clinically relevant causal pathogen. Characterization of functional differences among parasite species is confined to post hoc or single target studies, limiting the utility of this extrapolation approach. To address this challenge and to accelerate parasitology research broadly, we present a functional comparative analysis of 192 genomes, representing every high-quality, publicly-available protozoan parasite genome including Plasmodium, Toxoplasma, Cryptosporidium, Entamoeba, Trypanosoma, Leishmania, Giardia, and other species. We generated an automated metabolic network reconstruction pipeline optimized for eukaryotic organisms. These metabolic network reconstructions serve as biochemical knowledgebases for each parasite, enabling qualitative and quantitative comparisons of metabolic behavior across parasites. We identified putative differences in gene essentiality and pathway utilization to facilitate the comparison of experimental findings and discovered that phylogeny is not the sole predictor of metabolic similarity. This knowledgebase represents the largest collection of genome-scale metabolic models for both pathogens and eukaryotes; with this resource, we can predict species-specific functions, contextualize experimental results, and optimize selection of experimental systems for fastidious species.
Topics: Animals; Cryptosporidiosis; Cryptosporidium; Eukaryota; Genome, Protozoan; Parasites; Plasmodium
PubMed: 35196325
DOI: 10.1371/journal.pcbi.1009870 -
Genomics Mar 2022Nematodes are the most diverse but most minor studied microorganisms found in soil, water, animals, or plants. Either beneficial or pathogenic, they significantly affect... (Review)
Review
Nematodes are the most diverse but most minor studied microorganisms found in soil, water, animals, or plants. Either beneficial or pathogenic, they significantly affect human and animal health, plant production and ultimately affect the environmental equilibrium. Knowledge of their taxonomy and biology are the main issues to answer the different challenges associated with these microorganisms. The classical morphology-based nematode taxonomy and biodiversity studies have proved insufficient to identify closely related taxa and have challenged most biologists. Several molecular approaches have been used to supplement morphological methods and solve these problems with markable success. The molecular techniques range from enzyme analysis, protein-based information to DNA sequence analysis. For several decades, efforts have been made to integrate molecular approaches with digital 3D image-capturing technology to improve the identification accuracy of such a taxonomically challenging group and communicate morphological data. This review presents various molecular techniques and provides examples of recent advances in these methods to identify free-living and plant-parasitic nematodes.
Topics: Animals; Biodiversity; Nematoda; Parasites; Plants; Sequence Analysis, DNA
PubMed: 35134496
DOI: 10.1016/j.ygeno.2022.110295 -
Infection and Immunity Aug 2017Parasitic protozoan infections represent a major health burden in the developing world and contribute significantly to morbidity and mortality. These infections are... (Review)
Review
Parasitic protozoan infections represent a major health burden in the developing world and contribute significantly to morbidity and mortality. These infections are often associated with considerable variability in clinical presentation. An emerging body of work suggests that the intestinal microbiota may help to explain some of these differences in disease expression. The objective of this minireview is to synthesize recent progress in this rapidly advancing field. Studies of humans and animals and studies of the contribution of the intestinal microbiota to infectious disease are discussed. We hope to provide an understanding of the human-protozoal pathogen-microbiome interaction and to speculate on how that might be leveraged for treatment.
Topics: Animals; Gastrointestinal Microbiome; Host-Parasite Interactions; Humans; Parasites; Protozoan Infections
PubMed: 28584161
DOI: 10.1128/IAI.00101-17 -
Parasite (Paris, France) 2022Helminth parasitoses are among the most prevalent health issues worldwide. Their control depends largely on unravelling host-parasite interactions, including parasitic... (Review)
Review
Helminth parasitoses are among the most prevalent health issues worldwide. Their control depends largely on unravelling host-parasite interactions, including parasitic exploitation of the host haemostatic system. The present study undertakes a scoping review of the research carried out in this field with the aim of unifying and updating concepts. Multiple keywords combined with Boolean operators were employed to design the literature search strategy. Two online databases were used to identify original peer-reviewed articles written in English and published before 1st January 2020 describing molecular interactions between helminth parasites and the host haemostatic system. Relevant data from the selected sources of evidence were extracted and analysed. Ninety-six publications reporting 259 interactions were selected. Fifty-three proteins belonging to 32 species of helminth parasites were involved in interactions with components of the host haemostatic system. Many of these proteins from both parasite and host were conserved among the different interactions identified. Most of these interactions were related to the inhibition of the coagulation system and the activation of fibrinolysis. This was associated mainly with a potential of parasites to reduce the formation of blood clots in the host and attributed to biological processes, such as parasite nutrition, survival, invasion, evasion and migration or the appearance of pathological mechanisms in the host. A wide range of helminth parasites have developed similar strategies to exploit the haemostatic system of their hosts, which could be regarded as an evolutionary conserved mechanism that could confer benefits to parasites in terms of survival and establishment in their vertebrate hosts.
Topics: Animals; Helminths; Hemostatics; Host-Parasite Interactions; Parasites; Vertebrates
PubMed: 35833785
DOI: 10.1051/parasite/2022034 -
Memorias Do Instituto Oswaldo Cruz 2022Lipid droplets (LDs; lipid bodies) are intracellular sites of lipid storage and metabolism present in all cell types. Eukaryotic LDs are involved in eicosanoid...
Lipid droplets (LDs; lipid bodies) are intracellular sites of lipid storage and metabolism present in all cell types. Eukaryotic LDs are involved in eicosanoid production during several inflammatory conditions, including infection by protozoan parasites. In parasites, LDs play a role in the acquisition of cholesterol and other neutral lipids from the host. The number of LDs increases during parasite differentiation, and the biogenesis of these organelles use specific signaling pathways involving protein kinases. In addition, LDs are important in cellular protection against lipotoxicity. Recently, these organelles have been implicated in eicosanoid and specialised lipid metabolism. In this article, we revise the main functions of protozoan parasite LDs and discuss future directions in the comprehension of these organelles in the context of pathogen virulence.
Topics: Animals; Lipid Droplets; Lipid Metabolism; Parasites; Signal Transduction; Virulence
PubMed: 35195194
DOI: 10.1590/0074-02760210270 -
Parasitology Feb 2015SUMMARY From hundreds of independent transitions from a free-living existence to a parasitic mode of life, separate parasite lineages have converged over evolutionary... (Review)
Review
SUMMARY From hundreds of independent transitions from a free-living existence to a parasitic mode of life, separate parasite lineages have converged over evolutionary time to share traits and exploit their hosts in similar ways. Here, we first summarize the evidence that, at a phenotypic level, eukaryotic parasite lineages have all converged toward only six general parasitic strategies: parasitoid, parasitic castrator, directly transmitted parasite, trophically transmitted parasite, vector-transmitted parasite or micropredator. We argue that these strategies represent adaptive peaks, with the similarities among unrelated taxa within any strategy extending to all basic aspects of host exploitation and transmission among hosts and transcending phylogenetic boundaries. Then, we extend our examination of convergent patterns by looking at the evolution of parasite genomes. Despite the limited taxonomic coverage of sequenced parasite genomes currently available, we find some evidence of parallel evolution among unrelated parasite taxa with respect to genome reduction or compaction, and gene losses or gains. Matching such changes in parasite genomes with the broad phenotypic traits that define the convergence of parasites toward only six strategies of host exploitation is not possible at present. Nevertheless, as more parasite genomes become available, we may be able to detect clear trends in the evolution of parasitic genome architectures representing true convergent adaptive peaks, the genomic equivalents of the phenotypic strategies used by all parasites.
Topics: Animals; Biological Evolution; Ecology; Genomics; Host-Parasite Interactions; Parasites; Phylogeny
PubMed: 24229807
DOI: 10.1017/S0031182013001674 -
Parasitology Jun 2018X-ray micro-computed tomography (μCT) is a technique which can obtain three-dimensional images of a sample, including its internal structure, without the need for... (Review)
Review
X-ray micro-computed tomography (μCT) is a technique which can obtain three-dimensional images of a sample, including its internal structure, without the need for destructive sectioning. Here, we review the capability of the technique and examine its potential to provide novel insights into the lifestyles of parasites embedded within host tissue. The current capabilities and limitations of the technology in producing contrast in soft tissues are discussed, as well as the potential solutions for parasitologists looking to apply this technique. We present example images of the mouse whipworm Trichuris muris and discuss the application of μCT to provide unique insights into parasite behaviour and pathology, which are inaccessible to other imaging modalities.
Topics: Animals; Imaging, Three-Dimensional; Mice; Parasites; Trichuriasis; Trichuris; X-Ray Microtomography
PubMed: 29179788
DOI: 10.1017/S0031182017002074 -
Biochimica Et Biophysica Acta.... Oct 2021The proteins connexins, innexins, and pannexins are the subunits of non-selective channels present in the cell membrane in vertebrates (connexins and pannexins) and... (Review)
Review
The proteins connexins, innexins, and pannexins are the subunits of non-selective channels present in the cell membrane in vertebrates (connexins and pannexins) and invertebrates (innexins). These channels allow the transfer of ions and molecules across the cell membrane or, and in many cases, between the cytoplasm of neighboring cells. These channels participate in various physiological processes, particularly under pathophysiological conditions, such as bacterial, viral, and parasitic infections. Interestingly, some anti-parasitic drugs also block connexin- or pannexin-formed channels. Their effects on host channels permeable to molecules that favor parasitic infection can further explain the anti-parasitic effects of some of these compounds. In this review, the effects of drugs with known anti-parasitic activity that modulate non-selective channels formed by connexins or pannexins are discussed. Previous studies that have reported the presence of these proteins in worms, ectoparasites, and protozoa that cause parasitic infections have also been reviewed.
Topics: Animals; Antiparasitic Agents; Connexins; Gap Junctions; Humans; Parasites
PubMed: 34102257
DOI: 10.1016/j.bbadis.2021.166188 -
Trends in Parasitology May 2019Mathematical models play an increasingly important role in our understanding of the transmission and control of infectious diseases. Here, we present concrete examples... (Review)
Review
Mathematical models play an increasingly important role in our understanding of the transmission and control of infectious diseases. Here, we present concrete examples illustrating how mathematical models, paired with rigorous statistical methods, are used to parse data of different levels of detail and breadth and estimate key epidemiological parameters (e.g., transmission and its determinants, severity, impact of interventions, drivers of epidemic dynamics) even when these parameters are not directly measurable, when data are limited, and when the epidemic process is only partially observed. Finally, we assess the hurdles to be taken to increase availability and applicability of these approaches in an effort to ultimately enhance their public health impact.
Topics: Animals; Data Interpretation, Statistical; Epidemiologic Methods; Humans; Models, Theoretical; Parasitic Diseases; Parasitology
PubMed: 30738632
DOI: 10.1016/j.pt.2019.01.009