Misfolded proteins trapped in the endoplasmic reticulum (ER) are specifically recognized and retrotranslocated to the cytosol by the ER-Associated Degradation (ERAD) system and delivered to the proteasome for destruction. This process was recently described in Trypanosoma brucei (T. brucei) using the misfolded epitope tagged Transferrin Receptor subunits ESAG7:Ty and HA:ESAG6 (HA:E6). Critical to this

Proper targeting and secretion of lysosomal hydrolases are regulated by transporting receptors. Entamoeba histolytica, the enteric protozoan parasite responsible for human amebiasis, has a unique family of lysosomal hydrolase receptors, cysteine protease binding protein family, CPBF. CPBFs, consisting of 11 members with conserved domain organization, bind to a wide range of cargos including cysteine

Altering amounts of a protein in a cell has become a crucial tool for understanding its function. In many organisms, including the protozoan parasite Trypanosoma brucei, protein overexpression has been achieved by inserting a protein-coding sequence into an overexpression vector. Here, we have adapted the PCR only based system for tagging trypanosome proteins at their endogenous loci such that it in

The number of fully sequenced genomes increases steadily but the function of many genes remains unstudied. To accelerate dissection of gene function in Leishmania spp. and other kinetoplastids we previously developed a streamlined pipeline for CRISPR-Cas9 gene editing, which we termed LeishGEdit [1]. To facilitate high-throughput mutant screens we have adapted this pipeline by barcoding mutants with

Eggs, schistosomula and adult Schistosoma worms are known to release extracellular vesicles (EV) during in vitro incubations and these EVs are postulated to affect the host responses. So far only those EVs released during in vitro incubations of schistosomes have been studied and it is unknown whether in blood of infected hosts the schistosomal EVs can be detected amidst all the circulating EVs of

Codon usage bias (CUB) is the nonrandom usage of synonymous codons in which some codons are more preferred to others.CUB can be determined by mutation pressure and selection. Various approaches have been used to understand the pattern of CUB in the mitochondrial ND (MT-ND or ND) genes involved in complex I of respiratory chain in five different classes of Platyhelminthes as no work was reported yet

Defining protein-protein interactions is fundamental to the understanding of gene function. Protein-fragment complementation assays have been used for the analysis of protein-protein interactions in various organisms. The split-dihydrofolate reductase (DHFR) protein-fragment complementation assay utilises two complementary fragments of the enzyme fused to a pair of potentially interacting proteins

The lysine and glutamic acid rich protein KERP1 is a cell surface-expressed virulence factor in the human pathogen Entamoeba histolytica. It was originally suggested that the gene was absent from the related, avirulent human commensal Entamoeba dispar, an absence which would be relevant to the differential virulence of these species. Here, the gene is shown to be present in E. dispar, and its sequence

In free-living and parasitic nematodes, the methylation of phosphoethanolamine to phosphocholine provides a key metabolite to sustain phospholipid biosynthesis for growth and development. Because the phosphoethanolamine methyltransferases (PMT) of nematodes are essential for normal growth and development, these enzymes are potential targets of inhibitor design. The pine wilt nematode (Bursaphelenchus

The objective of this study was to analyze the mRNA transcription levels of ten functional genes of P-glycoproteins (P-gp) in free life stages, eggs and infective larvae (L3) and in endoparasitic stages, fourth larval stage (L4) and adult males of two native isolates of Haemonchus contortus: resistant and susceptible to IVM. The IVM resistant isolate was obtained from sheep naturally infected with

Trypanosoma brucei is an important human pathogen. In this study, we have focused on the characterization of FtsH protease, ATP-dependent membrane-bound mitochondrial enzyme important for regulation of protein abundance. We have determined localization and orientation of all six putative T.brucei FtsH homologs in the inner mitochondrial membrane by in silico analyses, by immunofluorescence, and with

Studies of Plasmodium sporozoites and liver stages require dissection of Anopheles mosquitoes to obtain sporozoites for experiments. Sporozoites from the rodent parasite P. yoelii are routinely used to infect hepatocytes for liver stage culture, but sometimes these cultures become contaminated. Using standard microbiological techniques, a single colony type of Gram-negative rod-shaped bacteria was

Conserved amongst all eukaryotes is a family of mitochondrial carrier proteins (SLC25A) responsible for the import of various solutes across the inner mitochondrial membrane. We previously reported that the human parasite Trypanosoma brucei possesses 26 SLC25A proteins (TbMCPs) amongst which two, TbMCP11 and TbMCP8, were predicted to function as phosphate importers. The transport of inorganic phosphate

The ACC-1 family of cys-loop receptors are ligand-gated chloride channels sensitive to acetylcholine (ACh), and are only present in invertebrates. Studies of this family of inhibitory receptors has provided insight into how they bind and respond to ACh in a manner vastly different from nicotinic acetylcholine receptors and appear to be present in tissues that are relevant to anthelmintic action. Here

Species of Centrorhynchus (Polymorphida: Centrorhynchidae) commonly parasitize various falconiform and strigiform birds worldwide. In the present study, the complete mitochondrial (mt) genome sequences of Centrorhynchus clitorideus was sequenced and annotated for the first time based on specimens collected from the little owl Athene noctua (Scopoli) (Strigiformes: Strigidae) in Pakistan. The complete

Translation initiation factor eIF4F is essential for cap-dependent translation initiation in eukaryotes. eIF4F is a trimeric complex consisting of a scaffold protein eIF4G, cap-binding protein eIF4E and DEAD-box RNA helicase eIF4A. eIF4F binds to the 5' cap structure of the mRNA through eIF4E and facilitates the binding of the preinitiation complex (PIC) via protein-protein interactions of eIF4G with

Trypanosoma are blood-borne parasites and are the causative agents of neglected tropical diseases (NTDs) affecting both humans and animals. These parasites mainly rely on glycolysis for their energy production within the mammalian host, which is why trypanosomal glycolytic enzymes have been pursued as interesting targets for the development of trypanocidal drugs. The structure-function relationships

Plasmodium parasites cause malaria in mammalian hosts and are transmitted by Anopheles mosquitoes. Gametocytes, which differentiate from asexual-stage parasites, are activated by environmental changes when ingested into the mosquito midgut, and are rapidly released from erythrocytes prior to fertilization. Secretory proteins localized to osmiophilic bodies (OBs), organelles unique to gametocytes, have

Helminth parasites secrete extracellular vesicles (EVs) into their environment that have potential roles in host-parasite communication, and thus represent potentially useful targets for novel control strategies. Here, we carried out a comprehensive proteomic analysis of two different populations of EVs - 15k pellet and 120k pellet EVs - from Schistosoma mansoni adult worms. We characterised the proteins

Copper is an essential component of cuproproteins but can be toxic to cells, therefore copper metabolism is very carefully regulated within cells. To gain insight into trypanosome copper metabolism, Trypanosoma spp. genomic databases were screened for the presence of copper-containing and -transporting proteins. Among other genes encoding copper-binding proteins, a copper-transporting P-type ATPase

The lysosomal cysteine protease activity of Trypanosoma brucei comprises a cathepsin B enzyme (TbCATB) and a cathepsin L enzyme (TbCATL). Inhibition of the cysteine protease activity is lethal to bloodstream-form trypanosomes but it was not entirely clear which of the two enzymes are essential for survival of the parasites. Here we show that the vinyl sulfone compound LU-102 selectively inhibits TbCATL

Galectins are among the most abundant excretory/secretory (ES) products of filarial worms, but their role in filarial biology is poorly understood. Galectin-2 (Lec-2), a major component of Brugia malayi extracellular vesicles, is released by filarial worms, and was recently identified in the serum of persons with loiasis. We therefore sought to clone and characterize Lec-2, and to develop reagents

ATP-Binding Cassette (ABC) transporters are proteins that actively mediate the transport of a wide variety of molecules, including drugs. Thus, in parasitology, ABC transporters have gained attention as potential targets for therapeutic drugs. Among the parasitic Platyhelminthes, ABC transporters have been identified and classified in a few species of Trematoda and Cestoda but not in Monogenea. Monogeneans

One of the most rapidly increasing human public health problems is obesity, whose sequelae like type-2 diabetes, represent continuously worsening, life-long conditions. Over the last 15 years, data have begun to emerge from human and more frequently, mouse studies, that support the idea that parasitic worm infection can protect against this condition. We have therefore investigated the potential of

Schistosomes are parasitic blood flukes that infect approximately 250 million people worldwide. The disease known as schistosomiasis, is the second most significant tropical parasitic disease after malaria. Praziquantel is the only effective drug currently licensed for schistosomiasis and there are concerns about resistance to the drug. There has been much effort to develop vaccines against schistosomiasis

Chitin, a homopolymer of β-(1,4) linked N-acetylglucosamine (GlcNAc), is a major component of cyst wall in the protozoan parasites Entamoeba histolytica (Eh) and Entamoeba invadens (Ei). The Entamoeba chitin synthase makes chitin at the vesicular membrane rather than the plasma membrane in fungi, even though the chemistry of chitin synthesis is most likely the same. However, the role of nucleotide

Entamoeba histolytica is an intestinal parasite infecting over 50 million people worldwide and is the causative agent of amebic dysentery and amoebic liver abscess. In the human host, E. histolytica experiences stress brought on by nutrient deprivation and the host immune response. To be a successful parasite, E. histolytica must counter the stress; therefore, understanding the stress response may

Similar to higher eukaryotes, the protist parasite T. brucei harbours several iron-containing proteins that regulate DNA and protein processing, oxidative stress defence and mitochondrial respiration. The synthesis of these proteins occurs either in the cytoplasm or within the mitochondrion. For mitochondrial iron cluster protein synthesis, iron needs to be transported across the solute impermeable

The CaaX proteases are closely related in the post-translational modification of many membrane-bound or secreted proteins and play a key role in the activation or stabilization of these molecules belonging to the CAAX family. In this study, a full-length cDNA putatively encoding a FACE-1/Ste24p CaaX protease (type I) of the Schistosoma japonicum was isolated. The cDNA, named SjSte24p, composed of 1646

The gastrointestinal (GI) tract of vertebrates is inhabited by a vast array of organisms, i.e., the microbiota and macrobiota. The former is composed largely of commensal microorganisms, which play vital roles in host nutrition and maintenance of energy balance, in addition to supporting the development and function of the vertebrate immune system. By contrast, the macrobiota includes parasitic helminths

Release of sporozoites from Eimeria oocysts/sporocysts is an essential step in the intracellular development of the parasite in its host. Little is known about this process except that elevated temperature (∼ 40 °C) plus trypsin and bile salts are required for sporozoite to escape from sporocysts. In this study, it was found that adding a reducing agent, either dithiothreitol (DTT) or Tris(2-carboxyethyl)phosphine

Nuclear receptors (NRs) belong to a large protein superfamily which includes intracellular receptors for secreted hydrophobic signal molecules, such as steroid hormones and thyroid hormones. They regulate development and reproduction in metazoans by binding to the promoter region of their target gene to activate or repress mRNA synthesis. Isolation and characterization of NRs in the parasitic trematode

The inhibitors produced by the parasitic worms successfully protect them from the host's proteases and are supposed to underlie the host-parasite specificity. Our previous study has shown that the extracts from the pike tapeworm Triaenophorus nodulosus inhibit host proteinases and commercial trypsin. We aimed to isolate and identify the components responsible for trypsin inactivation. After a two-step

Here we characterize a high-affinity Pi transport system energized by a H+ gradient in Leishmania amazonensis. Pi uptake and transcription of LamPho84 gene are differentially regulated during parasite life cycle. Our data suggest that Pi acquisition could be a pivotal task for the success of the parasite throughout its life cycle.

Chorismate synthase (Cs) is the last enzyme of the main trunk of shikimate pathway and catalyzes formation of chorismate, a major aromatic metabolite precursor. We have previously reported that Cs is highly conserved across different Plasmodium sp. Here we report that Cs from malaria parasites are bifunctional enzymes through expression and functional studies of two recombinant proteins rPfCs (Cs from

Toxoplasma gondii is a protozoan parasite that has a tremendous impact on human health and livestock. High seroprevalence among humans and other animals is facilitated by the conversion of rapidly proliferating tachyzoites into latent bradyzoites that are housed in tissue cysts, which allow transmission through predation. Epigenetic mechanisms contribute to the regulation of gene expression events

Mitochondrial respiration is a critical process for the survival of many eukaryotes, including parasites in the phylum Apicomplexa. These intracellular parasites include the causative agents of numerous serious diseases in humans and animals, including toxoplasmosis (Toxoplasma gondii) and malaria (Plasmodium species). Emerging evidence indicates that the mitochondrial respiratory chain of apicomplexans

Circulating miRNAs are stably existed in serum and plasma and can serve as a novel class of biomarkers for the diagnosis of helminthic infection. Fasciola gigantica, the causative agents of fascioliasis, live in the liver of in humans and ruminants, especially cattle, goat and sheep. In this study, a total of 121 host circulating miRNAs were differentially expressed (2 ≥ fold change, p < 0.05), of

Obesity and ancylostomiasis are considered public health problems. Recent studies have shown that infection by intestinal helminths in obese individuals can ameliorate metabolic disorder and improve glucose tolerance by decreasing both insulin resistance and low-intensity inflammation. However, few helminth species have been studied in this context, and some modulation mechanisms still require deeper

Here we report that trypanosomatid flagellates of the genus Blastocrithidia possess catalase. This enzyme is not phylogenetically related to the previously characterized catalases in other monoxenous trypanosomatids, suggesting that their genes have been acquired independently. Surprisingly, Blastocrithidia catalase is less enzymatically active, compared to its counterpart from Leptomonas pyrrhocoris

Plasmodium sporozoites are infective forms of the parasite to mammalian hepatocytes. Sporozoite surface or secreted proteins likely play an important role in recognition, invasion and successful establishment of hepatocyte infection. By approaches of reverse genetics, we report the functional analysis of two Plasmodium berghei (Pb) sporozoite specific genes- PbS10 and PbS23/SSP3 that encode for proteins

The salmon louse, Lepeophtheirus salmonis, is a hematophagous ectoparasite of salmonid fish. Due to its blood-feeding activity, the louse is exposed to great amounts of iron, which is an essential, yet potentially toxic mineral. The major known iron storage protein is ferritin, which the salmon louse encodes four genes of (LsFer1-4). Two of the ferritins are predicted to be secreted. These are one

Schistosoma mansoni is a long-lived intravascular trematode parasite that can infect humans causing the chronic debilitating disease, schistosomiasis. We hypothesize that the action of host-interactive proteins found at the schistosome surface allows the worms to maintain a safe, anti-thrombotic and anti-inflammatory environment around them in the bloodstream. One such protein is the ˜60 kDa alkaline

The MESA erythrocyte cytoskeleton binding (MEC) motif is a 13-amino acid sequence found in 14 exported Plasmodium falciparum proteins. First identified in the P. falciparum Mature-parasite-infected Erythrocyte Surface Antigen (MESA), the MEC motif is sufficient to target proteins to the infected red blood cell cytoskeleton. To identify host cell targets, purified MESA MEC motif was incubated with a

To survive within a red blood cell (RBC), malaria parasites establish striking modifications to the permeability, rigidity and cytoadherence properties of the host cell. This is mediated by the export of hundreds of proteins from the parasite into the erythrocyte. Plasmodium falciparum plasmepsin V (PfPMV), is an ER resident aspartic protease that processes proteins for export into the host erythrocyte

Nucleoside diphosphate kinases (NDPKs) are crucial to keep the high triphosphate nucleotide levels in the biological process. The enzymatic mechanism has been extensively described; however, the structural characteristics and kinetic parameters have never been fully determined. In Schistosoma mansoni, NDPK (SmNDPK) is directly involved in the pyrimidine and purine salvage pathways, being essential