Trypanosome

African Trypanosomiasis caused by trypanosome parasites continues to be a major neglected health problem, particularly in developing countries. Current treatments are marked by serious side effects, low effectiveness, high toxicity, and drug resistance prompting the need to develop novel, safe, effective, and alternative antitrypanosomal compounds. Anopyxis klaineana is an ethnomedicinal plant used in West Africa to treat many ailments including protozoan diseases. In this study, we investigated the antitrypanosomal potential of stem bark extracts of A...

Sterol biosynthesis via the mevalonate-isoprenoid pathway produces ergosterol (24β-methyl cholesta-5,7-dienol) necessary for growth in a wide-range of eukaryotic pathogenic organisms in eukaryotes, including the fungi, trypanosomes and amoebae, while their animal hosts synthesize a structurally less complicated product-cholesterol (cholest-5-enol). Because phyla-specific differences in sterol metabolizing enzyme architecture governs the binding and reaction properties of substrates and inhibitors while the order of sterol metabolizing enzymes involved in steroidogenesis determine the positioning of crucial chokepoint enzymes in the biosynthetic pathway, the selectivity and effectiveness of rationally designed ergosterol biosynthesis inhibitors toward ergosterol-dependent infectious diseases varies greatly...

The potential danger to livestock from African animal trypanosomiasis is well known. However, the trypanosome species circulating in cattle and their genetics are poorly understood. After different alignments according to three regions (ITS1, gGAPDH and rRNA gene) of the trypanosome genome, phylogenetic analyses were used to show the genetic diversity of the different species that were circulating in the cattle in three regions (Bagoue, Poro and Tchologo) of Côte d'Ivoire. These analyses were performed by alignment of ITS1; by alignment of partial 18S, ITS1, 5...

Trypanosomes are single-celled extracellular parasites that infect mammals, including humans and livestock, causing global public health concerns and economic losses. These parasites cycle between insect vectors, such as tsetse flies and vertebrate hosts, undergoing morphological, cellular, and biochemical changes. They have remarkable immune evasion mechanisms to escape the host's innate and adaptive immune responses, such as surface coat antigenic variation and the induction of the loss of specificity and memory of antibody responses, enabling the prolongation of infection...

In the respiratory chain of the majority of aerobic organisms, the enzyme alternative oxidase (AOX) functions as the terminal oxidase and has important roles in maintaining metabolic and signaling homeostasis in mitochondria. AOX endows the respiratory system with flexibility in the coupling among the carbon metabolism pathway, electron transport chain (ETC) activity, and ATP turnover. AOX allows electrons to bypass the main cytochrome pathway to restrict the generation of reactive oxygen species (ROS). The inhibition of AOX leads to oxidative damage and contributes to the loss of adaptability and viability in some pathogenic organisms...

Trypanosoma brucei gambiense (Tbg) group 2 is a subgroup of trypanosomes able to infect humans and is found in West and Central Africa. Unlike other agents causing sleeping sickness, such as Tbg group 1 and Trypanosoma brucei rhodesiense, Tbg2 lacks the typical molecular markers associated with resistance to human serum. Only 36 strains of Tbg2 have been documented, and therefore, very limited research has been conducted despite their zoonotic nature. Some of these strains are only available in their procyclic form, which hinders human serum resistance assays and mechanistic studies...

Suramin was the first effective drug for the treatment of human African sleeping sickness. Structural analogues of the trypanocide have previously been shown to be potent inhibitors of several enzymes. Therefore, four suramin analogues lacking the methyl group on the intermediate rings and with different regiochemistry of the naphthalenetrisulphonic acid groups and the phenyl rings were tested to establish whether they exhibited improved antiproliferative activity against bloodstream forms of Trypanosomes brucei compared to the parent compound...

African animal trypanosomosis is a parasitic disease that causes significant economic losses in livestock due to anaemia, loss of condition, emaciation, and mortality. It is a key impediment to increased cattle output and productivity in Ethiopia. Cross-sectional entomological and parasitological studies were performed in the Gambella Region state of southwestern Ethiopia to estimate the prevalence of bovine trypanosomosis, apparent fly density, and potential risk factors. Blood samples were taken from 546 cattle for the parasitological study and analyzed using the buffy coat technique and stained with Giemsa...

Trypanosomatid parasites are kinetoplastid protists that compartmentalize glycolytic enzymes in unique peroxisome-related organelles called glycosomes. The heterohexameric AAA-ATPase complex of PEX1-PEX6 is anchored to the peroxisomal membrane and functions in the export of matrix protein import receptor PEX5 from the peroxisomal membrane. Defects in PEX1, PEX6 or their membrane anchor causes dysfunction of peroxisomal matrix protein import cycle. In this study, we functionally characterized a putative Trypanosoma PEX1 orthologue by bioinformatic and experimental approaches and show that it is a true PEX1 orthologue...

The hemoparasite Trypanosoma equiperdum belongs to the Trypanozoon subgenus and includes several species that are pathogenic to animals and humans in tropical and subtropical areas across the world. As with all eukaryotic organisms, Ca2+ is essential for these parasites to perform cellular processes thus ensuring their survival across their life cycle. Despite the established paradigm to study proteins related to Ca2+ homeostasis as potential drug targets, so far little is known about Ca2+ entry into trypanosomes...

Significant variations in the abundance of mitochondrial RNA processing proteins and their target RNAs across trypanosome life stages present an opportunity to explore the regulatory mechanisms that drive these changes. Utilizing omics approaches can uncover unconventional targets, aiding our understanding of the parasites' adaptation and enabling targeted interventions for differentiation.

Human African Trypanosomiasis (HAT) is a neglected parasitic disease that continues to persist in sub-Saharan Africa. It is fatal if untreated. The first stage of the disease is associated with the presence of the parasite in the periphery and the second stage with the presence of the parasites in the CNS. The treatment of CNS stage HAT requires the drugs to cross the blood-brain barrier (BBB). Eflornithine is an amino acid analogue that is used to treat second stage HAT gambiense both alone and in combination with nifurtimox...

The functions of human Apolipoproteins L (APOLs) are poorly understood, but involve diverse activities like lysis of bloodstream trypanosomes and intracellular bacteria, modulation of viral infection and induction of apoptosis, autophagy, and chronic kidney disease. Based on recent work, I propose that the basic function of APOLs is the control of membrane dynamics, at least in the Golgi and mitochondrion. Together with neuronal calcium sensor-1 (NCS1) and calneuron-1 (CALN1), APOL3 controls the activity of phosphatidylinositol-4-kinase-IIIB (PI4KB), involved in both Golgi and mitochondrion membrane fission...

BACKGROUND: The gene variants ADH1B*2 (Arg48His, rs1229984) and ALDH2*2 (Glu504Lys, rs671) are common in East Asian populations but rare in other populations. We propose that selective pressures from pathogen exposure and dietary changes during the neolithic transition favored these variants. Thus, their current association with differences in alcohol sensitivity likely results from phenotypic plasticity rather than direct natural selection. METHODS: Samples sourced from the Allele Frequency Database (ALFRED) were utilized to compute the average frequency of ADH1B*2 and ALDH2*2 across 88 and 61 countries, respectively...

Earlier evidences showed that diglycosyl diselenides are active against the infective stage of African trypanosomes (top hits IC50 0.5 and 1.5 μM) but poorly selective (selectivity index <10). Here we extended the study to 33 new seleno-glycoconjugates with the aim to improve potency and selectivity. Three selenoglycosides and three glycosyl selenenylsulfides displayed IC50 against bloodstream Trypanosoma brucei in the sub-μM range (IC50 0.35-0.77 μM) and four of them showed an improved selectivity (selectivity index >38-folds vs...

Parasitic organisms pose a major global health threat, mainly in regions that lack advanced medical facilities. Early and accurate detection of parasitic organisms is vital to saving lives. Deep learning models have uplifted the medical sector by providing promising results in diagnosing, detecting, and classifying diseases. This paper explores the role of deep learning techniques in detecting and classifying various parasitic organisms. The research works on a dataset consisting of 34,298 samples of parasites such as Toxoplasma Gondii, Trypanosome, Plasmodium, Leishmania, Babesia, and Trichomonad along with host cells like red blood cells and white blood cells...

Parasites play a pivotal role in ecosystem health, influencing human and zoonotic diseases, as well as biodiversity preservation. The genus Trypanosoma comprises approximately 500 species mostly found in wildlife animals. This study focuses on identifying trypanosomes found in the white-necked thrush (Turdus albicollis) and the yellow-legged thrush (Turdus flavipes) in the Neotropics. First, we demonstrate the utility of an 18S rDNA sequence-structure phylogeny as an alternative method for trypanosome classification, especially when gGAPDH sequences are unavailable...

KKT4 is a multi-domain kinetochore protein specific to kinetoplastids, such as Trypanosoma brucei. It lacks significant sequence similarity to known kinetochore proteins in other eukaryotes. Our recent X-ray structure of the C-terminal region of KKT4 shows that it has a tandem BRCT (BRCA1 C Terminus) domain fold with a sulfate ion bound in a typical binding site for a phosphorylated serine or threonine. Here we present the 1 H, 13 C and 15 N resonance assignments for the BRCT domain of KKT4 (KKT4463-645 ) from T...

BACKGROUND: African sleeping sickness is a neglected tropical disease seldom seen in European travellers. CASE PRESENTATION: While working in Eastern Africa, a Norwegian man in his sixties developed weakness and fever. He was prescribed doxycycline after a negative malaria rapid test. On the third day of illness he returned to Norway and was admitted to the hospital upon arrival. On admission he was somnolent with fever, tachypnoea, tachycardia, jaundice, a hyperaemic rash, oliguria and haematuria...

Tsetse flies (genus Glossina) transmit deadly trypanosomes to human populations and domestic animals in sub-Saharan Africa. Some foci of Human African Trypanosomiasis due to Trypanosoma brucei gambiense (g-HAT) persist in southern Chad, where a program of tsetse control was implemented against the local vector Glossina fuscipes fuscipes in 2018 in Maro. We analyzed the population genetics of G. f. fuscipes from the Maro focus before control (T0), one year (T1), and 18 months (T2) after the beginning of control efforts...