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Background Protists of the family Trypanosomatidae (phylum Euglenozoa) have gained notoriety as parasites affecting humans, domestic animals, and agricultural plants. However, the true extent of the group's diversity spreads far beyond the medically and veterinary relevant species. We address several knowledge gaps in trypanosomatid research by undertaking sequencing, assembly, and analysis of genomes from previously overlooked representatives of this protistan group. Results We assembled genomes for twenty-one trypanosomatid species, with a primary focus on insect parasites and Trypanosoma spp. parasitizing non-human hosts. The assemblies exhibit sizes consistent with previously sequenced trypanosomatid genomes, ranging from approximately 18 Mb for Obscuromonas modryi to 35 Mb for Crithidia brevicula and Zelonia costaricensis . Despite being the smallest, the genome of O. modryi has the highest content of repetitive elements, contributing nearly half of its total size. Conversely, the highest proportion of unique DNA is found in the genomes of Wallacemonas spp., with repeats accounting for less than 8% of the assembly length. The majority of examined species exhibit varying degrees of aneuploidy, with trisomy being the most frequently observed condition after disomy. Conclusions The genome of Obscuromonas modryi represents a very unusual, if not unique, example of evolution driven by two antidromous forces: i) increasing dependence on the host leading to genomic shrinkage and ii) expansion of repeats causing genome enlargement. The observed variation in somy within and between trypanosomatid genera suggests that these flagellates are largely predisposed to aneuploidy and, apparently, exploit it to gain a fitness advantage. High heterogeneity in the genome size, repeat content, and variation in chromosome copy numbers in the newly-sequenced species highlight the remarkable genome plasticity exhibited by trypanosomatid flagellates. These new genome assemblies are a robust foundation for future research on the genetic basis of life cycle changes and adaptation to different hosts in the family Trypanosomatidae.

Honey bees, and pollinators in general, play a major role in the health of ecosystems. There is a consensus about the steady decrease in pollinator populations, which raises global ecological concern. Several drivers are implicated in this threat. Among them, honey bee pathogens are transmitted to other arthropods populations, including wild and managed pollinators. The western honey bee, Apis mellifera, is quasi-globally spread. This successful species acted as and, in some cases, became a maintenance host for pathogens. This systematic review collects and summarizes spillover cases having in common Apis mellifera as the mainteinance host and some of its pathogens. The reports are grouped by final host species and condition, year, and geographic area of detection and the co-occurrence in the same host. A total of eighty-one articles in the time frame 1960–2021 were included. The reported spillover cases cover a wide range of hymenopteran host species, generally living in close contact with or sharing the same environmental resources as the honey bees. They also involve non-hymenopteran arthropods, like spiders and roaches, which are either likely or unlikely to live in close proximity to honey bees. Specific studies should consider host-dependent pathogen modifications and effects on involved host species. Both the plasticity of bee pathogens and the ecological consequences of spillover suggest a holistic approach to bee health and the implementation of a One Health approach.

Trypanosomatids constitute a family of parasitic protozoa that cause significant human and veterinary diseases that are classified as neglected zoonotic diseases (NZDs). In a rapidly evolving world, these diseases have the potential to become a world health problem no longer solely associated with low-income countries. Therefore, the development of new strategies to control and restrain the dissemination of trypanosomatids is imperative. Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed vesicles released by prokaryotic and eukaryotic cells. They can be found in diverse body fluids that carry biologically active molecules, including proteins, nucleic acids, lipids, and carbohydrates. EVs participate in cell-to-cell communication by delivering their cargo content to recipient cells. Thus, EVs play a role in regulating normal physiological processes, including immune surveillance and tissue repair, as well as being involved in pathological conditions, like cancer. In recent years, EVs have attracted significant attention from the scientific community, mainly due to their immune regulatory properties. Therefore, this review examines the role played by trypanosomatid-derived EVs in leishmaniases and trypanosomiasis, highlighting their biological role in host–parasite communication and exploring their potential future applications in controlling NZDs, especially those caused by trypanosomatids.

Infectious diseases caused by trypanosomatids, including African trypanosomiasis (sleeping sickness), Chagas disease, and different forms of leishmaniasis, are Neglected Tropical Diseases affecting millions of people worldwide, mainly in vulnerable territories of tropical and subtropical areas. In general, current treatments against these diseases are old-fashioned, showing adverse effects and loss of efficacy due to misuse or overuse, thus leading to the emergence of resistance. For these reasons, searching for new antitrypanosomatid drugs has become an urgent necessity, and different metabolic pathways have been studied as potential drug targets against these parasites. Considering that trypanosomatids possess a unique redox pathway based on the trypanothione molecule absent in the mammalian host, the key enzymes involved in trypanothione metabolism, trypanothione reductase and trypanothione synthetase, have been studied in detail as druggable targets. In this review, we summarize some of the recent findings on the molecules inhibiting these two essential enzymes for Trypanosoma and Leishmania viability.

Fatty acids have received growing interest in Leishmania biology with the characterization of the enzymes allowing the complete fatty acid synthesis of this trypanosomatid parasite. This review presents a comparative analysis of the fatty acid profiles of the major classes of lipids and phospholipids in different species of Leishmania with cutaneous or visceral tropism. Specificities relating to the parasite forms, resistance to antileishmanial drugs, and host/parasite interactions are described as well as comparisons with other trypanosomatids. Emphasis is placed on polyunsaturated fatty acids and their metabolic and functional specificities, in particular, their conversion into oxygenated metabolites that are inflammatory mediators able to modulate metacyclogenesis and parasite infectivity. The impact of lipid status on the development of leishmaniasis and the potential of fatty acids as therapeutic targets or candidates for nutritional interventions are discussed.

Dithiocarbamates represent a class of compounds that were evaluated in different biomedical applications because of their chemical versatility. For this reason, several pharmacological activities have already been attributed to these compounds, such as antiparasitic, antiviral, antifungal activities, among others. Therefore, compounds that are based on dithiocarbamates have been evaluated in different in vivo and in vitro models as potential new antimicrobials. Thus, the purpose of this review is to present the possibilities of using dithiocarbamate compounds as potential new antitrypanosomatids-drugs, which could be used for the pharmacological control of Chagas disease, leishmaniasis, and African trypanosomiasis.

Complex I (NADH dehydrogenase) is the first enzyme in the respiratory chain. It catalyses the electron transfer from NADH to ubiquinone that is associated with proton pumping out of the matrix. In this study, we characterized NADH dehydrogenase activity in seven monoxenous trypanosomatid species: Blechomonas ayalai, Herpetomonas tarakana, Kentomonas sorsogonicus, Leptomonas seymouri, Novymonas esmeraldas, Sergeia podlipaevi and Wallacemonas raviniae. We also investigated the subunit composition of the complex I in dixenous Phytomonas serpens, in which its presence and activity have been previously documented. In addition to P. serpens, the complex I is functionally active in N. esmeraldas and S. podlipaevi. We also identified 24–32 subunits of the complex I in individual species by using mass spectrometry. Among them, for the first time, we recognized several proteins of the mitochondrial DNA origin.

The protozoans Leishmania and Trypanosoma, belonging to the same Trypanosomatidae family, are the causative agents of Leishmaniasis, Chagas disease, and human African trypanosomiasis. Overall, these infections affect millions of people worldwide, posing a serious health issue as well as socio-economical concern. Current treatments are inadequate, mainly due to poor efficacy, toxicity, and emerging resistance; therefore, there is an urgent need for new drugs. Among several molecular targets proposed, trypanothione reductase (TR) is of particular interest for its critical role in controlling the parasite’s redox homeostasis and several classes of active compounds that inhibit TR have been proposed so far. This review provides a comprehensive overview of TR’s structural characterization. In particular, we discuss all the structural features of TR relevant for drug discovery, with a focus on the recent advances made in the understanding of inhibitor binding. The reported cases show how, on the basis of the detailed structural information provided by the crystallographic analysis, it is possible to rationally modify molecular scaffolds to improve their properties.

There is no effective cure for Chagas disease, which is caused by infection with the arthropod-borne parasite, . In the search for new drugs to treat Chagas disease, potential therapeutic targets have been identified by exploiting the differences between the mechanisms involved in intracellular Ca homeostasis, both in humans and in trypanosomatids. In the trypanosomatid, intracellular Ca regulation requires the concerted action of three intracellular organelles, the endoplasmic reticulum, the single unique mitochondrion, and the acidocalcisomes. The single unique mitochondrion and the acidocalcisomes also play central roles in parasite bioenergetics. At the parasite plasma membrane, a Ca - ATPase (PMCA) with significant differences from its human counterpart is responsible for Ca extrusion; a distinctive sphingosine-activated Ca channel controls Ca entrance to the parasite interior. Several potential anti-trypansosomatid drugs have been demonstrated to modulate one or more of these mechanisms for Ca regulation. The antiarrhythmic agent amiodarone and its derivatives have been shown to exert trypanocidal effects through the disruption of parasite Ca homeostasis. Similarly, the amiodarone-derivative dronedarone disrupts Ca homeostasis in epimastigotes, collapsing the mitochondrial membrane potential (ΔΨ ), and inducing a large increase in the intracellular Ca concentration ([Ca ] ) from this organelle and from the acidocalcisomes in the parasite cytoplasm. The same general mechanism has been demonstrated for SQ109, a new anti-tuberculosis drug with potent trypanocidal effect. Miltefosine similarly induces a large increase in the [Ca ] acting on the sphingosine-activated Ca channel, the mitochondrion and acidocalcisomes. These examples, in conjunction with other evidence we review herein, strongly support targeting Ca homeostasis as a strategy against Chagas disease.

Trypanosomatids are obligate parasites of animals, predominantly insects and vertebrates, and flowering plants. Monoxenous species, representing the vast majority of trypanosomatid diversity, develop in a single host, whereas dixenous species cycle between two hosts, of which primarily insect serves as a vector. To explore in-depth the diversity of insect trypanosomatids including their co-infections, sequence profiling of their 18S rRNA gene was used for true bugs (Hemiptera; 18% infection rate) and flies (Diptera; 10%) in Cuba. Out of 48 species (molecular operational taxonomic units) belonging to the genera Vickermania (16 spp.), Blastocrithidia (7), Obscuromonas (4), Phytomonas (5), Leptomonas/Crithidia (5), Herpetomonas (5), Wallacemonas (2), Kentomonas (1), Angomonas (1) and two unnamed genera (1 + 1), 38 species have been encountered for the first time. The detected Wallacemonas and Angomonas species constitute the most basal lineages of their respective genera, while Vickermania emerged as the most diverse group. The finding of Leptomonas seymouri, which is known to rarely infect humans, confirms that Dysdercus bugs are its natural hosts. A clear association of Phytomonas with the heteropteran family Pentatomidae hints at its narrow host association with the insect rather than plant hosts. With a focus on multiple infections of a single fly host, using deep Nanopore sequencing of 18S rRNA, we have identified co-infections with up to 8 trypanosomatid species. The fly midgut was usually occupied by several Vickermania species, while Herpetomonas and/or Kentomonas species prevailed in the hindgut. Metabarcoding was instrumental for analysing extensive co-infections and also allowed the identification of trypanosomatid lineages and genera.