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Nucleic Acids Research Jan 2022The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As...
The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC.
Topics: Animals; Apicomplexa; Bacteria; Communicable Diseases; Computational Biology; Data Mining; Databases, Factual; Diplomonadida; Disease Vectors; Fungi; Host-Pathogen Interactions; Humans; Insecta; Internet; Nematoda; Phenotype; Phylogeny; User-Computer Interface; Virulence; Workflow
PubMed: 34718728
DOI: 10.1093/nar/gkab929 -
Experimental Parasitology Jul 2022Toxoplasma gondii, as other apicomplexa, employs adhesins transmembrane proteins for binding and invasion to host cells. Search and characterization of adhesins is...
Toxoplasma gondii, as other apicomplexa, employs adhesins transmembrane proteins for binding and invasion to host cells. Search and characterization of adhesins is pivotal in understanding Apicomplexa invasion mechanisms and targeting new druggable candidates. This work developed a machine learning software called ApiPredictor UniQE V2.0, based on two approaches: support vector machines and multilayer perceptron, to predict adhesins proteins from amino acid sequences. By using ApiPredictor UniQE V2.0, five SAG-Related Sequences (SRSs) were identified within the Toxoplasma gondii proteome. One of those candidates, TgSRS12B, was cloned in plasmid pEXP5-CT/TOPO and expressed in E. coli BL21 DE3. The resulting recombinant protein was purified via affinity chromatography. Co-precipitation assays in CaCo and Muller cells showed interactions between TgSRS12B-His-tagged and the membrane fractions from both human cell lines. In conclusion, we demonstrated that ApiPredictor UniQE V2.0, a bioinformatic free software, was able to identify TgSRS12B as a new adhesin protein.
Topics: Escherichia coli; Humans; Machine Learning; Plasmids; Protozoan Proteins; Toxoplasma
PubMed: 35460696
DOI: 10.1016/j.exppara.2022.108261 -
Frontiers in Cellular and Infection... 2020Apicomplexan parasites, such as human malaria parasites, have complex lifecycles encompassing multiple and diverse environmental niches. Invading, replicating, and... (Review)
Review
Apicomplexan parasites, such as human malaria parasites, have complex lifecycles encompassing multiple and diverse environmental niches. Invading, replicating, and escaping from different cell types, along with exploiting each intracellular niche, necessitate large and dynamic changes in parasite morphology and cellular architecture. The inner membrane complex (IMC) is a unique structural element that is intricately involved with these distinct morphological changes. The IMC is a double membrane organelle that forms and is located beneath the plasma membrane of these single-celled organisms. In spp. parasites it has three major purposes: it confers stability and shape to the cell, functions as an important scaffolding compartment during the formation of daughter cells, and plays a major role in motility and invasion. Recent years have revealed greater insights into the architecture, protein composition and function of the IMC. Here, we discuss the multiple roles of the IMC in each parasite lifecycle stage as well as insights into its sub-compartmentalization, biogenesis, disassembly and regulation during stage conversion of .
Topics: Animals; Cell Membrane; Humans; Malaria; Parasites; Plasmodium; Plasmodium falciparum; Protozoan Proteins
PubMed: 33489940
DOI: 10.3389/fcimb.2020.611801 -
Molecular and Biochemical Parasitology Sep 2024Apicomplexan parasites are the primary causative agents of many human diseases, including malaria, toxoplasmosis, and cryptosporidiosis. These opportunistic pathogens... (Review)
Review
Apicomplexan parasites are the primary causative agents of many human diseases, including malaria, toxoplasmosis, and cryptosporidiosis. These opportunistic pathogens undergo complex life cycles with multiple developmental stages, wherein many key steps are regulated by phosphorylation mechanisms. The genomes of apicomplexan pathogens contain protein kinases from different groups including tyrosine kinase-like (TKL) family proteins. Although information on the role of TKL kinases in apicomplexans is quite limited, recent studies have revealed the important role of this family of proteins in apicomplexan biology. TKL kinases in these protozoan pathogens show unique organization with many novel domains thus making them attractive candidates for drug development. In this mini review, we summarize the current understanding of the role of TKL kinases in human apicomplexan pathogens' (Toxoplasma gondii, Plasmodium falciparum and Cryptosporidium parvum) biology and pathogenesis.
Topics: Humans; Toxoplasma; Cryptosporidium parvum; Protozoan Proteins; Plasmodium falciparum; Apicomplexa; Protein-Tyrosine Kinases; Phosphorylation
PubMed: 38719028
DOI: 10.1016/j.molbiopara.2024.111628 -
Parasitology Aug 2018Although the application of CRISPR/Cas9 genome engineering approaches was first reported in apicomplexan parasites only 3 years ago, this technology has rapidly become... (Review)
Review
Although the application of CRISPR/Cas9 genome engineering approaches was first reported in apicomplexan parasites only 3 years ago, this technology has rapidly become an essential component of research on apicomplexan parasites. This review briefly describes the history of CRISPR/Cas9 and the principles behind its use along with documenting its implementation in apicomplexan parasites, especially Plasmodium spp. and Toxoplasma gondii. We also discuss the recent use of CRISPR/Cas9 for whole genome screening of gene knockout mutants in T. gondii and highlight its use for seminal genetic manipulations of Cryptosporidium spp. Finally, we consider new variations of CRISPR/Cas9 that have yet to be implemented in apicomplexans. Whereas CRISPR/Cas9 has already accelerated rapid interrogation of gene function in apicomplexans, the full potential of this technology is yet to be realized as new variations and innovations are integrated into the field.
Topics: Animals; Apicomplexa; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Cryptosporidium; Gene Knockout Techniques; Genetic Engineering; Genome, Protozoan; Humans; Mice; Plasmodium; Recombination, Genetic; Toxoplasma
PubMed: 29463318
DOI: 10.1017/S003118201800001X -
International Journal For Parasitology May 2020Toxoplasma gondii is remarkably unique in its ability to successfully infect vertebrate hosts from multiple phyla and can successfully infect most cells within these... (Review)
Review
Toxoplasma gondii is remarkably unique in its ability to successfully infect vertebrate hosts from multiple phyla and can successfully infect most cells within these organisms. The infection outcome in each of these species is determined by the complex interaction between parasite and host genotype. As techniques to quantify global changes in cell function become more readily available and precise, new data are coming to light about how (i) different host cell types respond to parasitic infection and (ii) different parasite species impact the host. Here we focus on recent studies comparing the response to intracellular parasitism by different cell types and insights into understanding host-parasite interactions from comparative studies on T. gondii and its close extant relatives.
Topics: Animals; Apicomplexa; Biological Evolution; Cell Line; Chemokines; Coccidiosis; Gene Expression; Host Specificity; Host-Parasite Interactions; Humans; Immunity; Interferon-gamma; Mammals; Neospora; Protein Serine-Threonine Kinases; Protozoan Proteins; THP-1 Cells; Toxoplasma; Toxoplasmosis; Transcriptome; Tumor Suppressor Protein p53; Virulence
PubMed: 32407716
DOI: 10.1016/j.ijpara.2020.05.001 -
Folia Parasitologica Jun 2017A total of 345 faecal samples were collected from domestic, captive and wild birds in rural areas, urban areas and a Zoo in Algeria. Samples were screened for the...
A total of 345 faecal samples were collected from domestic, captive and wild birds in rural areas, urban areas and a Zoo in Algeria. Samples were screened for the presence of parasites belonging to the genus Cryptosporidium Tyzzer, 1910 by microscopy and PCR analysis of the small-subunit rRNA (SSU), actin and 60-kDa glycoprotein (gp60) genes. Cryptosporidium spp. were detected in 31 samples. Sequence analysis of SSU and actin genes revealed the presence of C. baileyi Current, Upton et Haynes, 1986 in domestic chicken broilers (n = 12), captive ostriches (n = 4) and a wild mallard (n = 1), and C. meleagridis Slavin, 1955 in a graylag goose (n = 1), chickens (n = 11) and turkeys (n = 2). Twenty-three chicken and two turkey broilers from five farms were positive for cryptosporidia, with an overall prevalence of 2% and 6%, respectively. Both C. meleagridis and C. baileyi were detected in farmed chicken broilers, with a prevalence ranging from 9% to 69%. Farmed turkeys broilers were positive only for C. meleagridis, with a 13% prevalence at the animal level. Subtyping of C. meleagridis isolates at the gp60 locus showed the presence of subtype IIIgA22G3R1 in graylag goose and chicken broilers and IIIgA23G2R1 in chicken and turkey broilers. Infection with cryptosporidia was not associated with any clinical diseases. The results of the present study, which provides the first data on the prevalence of Cryptosporidium spp. in wild birds in Africa, demonstrate the presence of human pathogenic C. meleagridis in both domestic and wild birds in Algeria.
Topics: Algeria; Animals; Bird Diseases; Birds; Chickens; Cryptosporidiosis; Cryptosporidium; Feces; Phylogeny; Poultry Diseases
PubMed: 28620152
DOI: 10.14411/fp.2017.018 -
International Journal of Molecular... Nov 2019Obligate protozoan parasites of the kinetoplastids and apicomplexa infect human cells to complete their life cycles. Some of the members of these groups of parasites... (Review)
Review
Obligate protozoan parasites of the kinetoplastids and apicomplexa infect human cells to complete their life cycles. Some of the members of these groups of parasites develop in at least two systems, the human host and the insect vector. Survival under the varied physiological conditions associated with the human host and in the arthropod vectors requires the parasites to modulate their metabolic complement in order to meet the prevailing conditions. One of the key features of these parasites essential for their survival and host infectivity is timely expression of various proteins. Even more importantly is the need to keep their proteome functional by maintaining its functional capabilities in the wake of physiological changes and host immune responses. For this reason, molecular chaperones (also called heat shock proteins)-whose role is to facilitate proteostasis-play an important role in the survival of these parasites. Heat shock protein 90 (Hsp90) and Hsp70 are prominent molecular chaperones that are generally induced in response to physiological stress. Both Hsp90 and Hsp70 members are functionally regulated by nucleotides. In addition, Hsp70 and Hsp90 cooperate to facilitate folding of some key proteins implicated in cellular development. In addition, Hsp90 and Hsp70 individually interact with other accessory proteins (co-chaperones) that regulate their functions. The dependency of these proteins on nucleotide for their chaperone function presents an Achille's heel, as inhibitors that mimic ATP are amongst potential therapeutic agents targeting their function in obligate intracellular human parasites. Most of the promising small molecule inhibitors of parasitic heat shock proteins are either antibiotics or anticancer agents, whose repurposing against parasitic infections holds prospects. Both cancer cells and obligate human parasites depend upon a robust protein quality control system to ensure their survival, and hence, both employ a competent heat shock machinery to this end. Furthermore, some inhibitors that target chaperone and co-chaperone networks also offer promising prospects as antiparasitic agents. The current review highlights the progress made so far in design and application of small molecule inhibitors against obligate intracellular human parasites of the kinetoplastida and apicomplexan kingdoms.
Topics: Apicomplexa; Euglenozoa Infections; Heat-Shock Proteins; Humans; Kinetoplastida; Proteostasis; Protozoan Infections; Small Molecule Libraries
PubMed: 31775392
DOI: 10.3390/ijms20235930 -
Nature Communications Jan 2024In Apicomplexa, rhoptry discharge is essential for invasion and involves an apical vesicle (AV) docking one or two rhoptries to a macromolecular secretory apparatus....
In Apicomplexa, rhoptry discharge is essential for invasion and involves an apical vesicle (AV) docking one or two rhoptries to a macromolecular secretory apparatus. Toxoplasma gondii is armed with 10-12 rhoptries and 5-6 microtubule-associated vesicles (MVs) presumably for iterative rhoptry discharge. Here, we have addressed the localization and functional significance of two intraconoidal microtubule (ICMT)-associated proteins instrumental for invasion. Mechanistically, depletion of ICMAP2 leads to a dissociation of the ICMTs, their detachment from the conoid and dispersion of MVs and rhoptries. ICMAP3 exists in two isoforms that contribute to the control of the ICMTs length and the docking of the two rhoptries at the AV, respectively. This study illuminates the central role ICMTs play in scaffolding the discharge of multiple rhoptries. This process is instrumental for virulence in the mouse model of infection and in addition promotes sterile protection against T. gondii via the release of key effectors inducing immunity.
Topics: Animals; Mice; Toxoplasma; Microtubule-Associated Proteins; Cytoskeleton; Microtubules; Biological Transport
PubMed: 38191574
DOI: 10.1038/s41467-023-44631-y -
Frontiers in Cellular and Infection... 2022
Topics: Animals; Apicomplexa; Cell Communication; Parasites; Protozoan Infections
PubMed: 35685751
DOI: 10.3389/fcimb.2022.930073