-
Parasites & Vectors Apr 2019African trypanosomes cause human African trypanosomiasis and animal African trypanosomiasis. They are transmitted by tsetse flies in sub-Saharan Africa. Although most...
African trypanosomes cause human African trypanosomiasis and animal African trypanosomiasis. They are transmitted by tsetse flies in sub-Saharan Africa. Although most famous for their mechanisms of immune evasion by antigenic variation, there have been recent important studies that illuminate important aspects of the biology of these parasites both in their mammalian host and during passage through their tsetse fly vector. This Primer overviews current research themes focused on these parasites and discusses how these biological insights and the development of new technologies to interrogate gene function are being used in the search for new approaches to control the parasite. The new insights into the biology of trypanosomes in their host and vector highlight that we are in a 'golden age' of discovery for these fascinating parasites.
Topics: Africa South of the Sahara; Animals; Host-Parasite Interactions; Humans; Insect Vectors; Trypanosoma; Trypanosoma brucei brucei; Trypanosomiasis, African; Tsetse Flies
PubMed: 31036044
DOI: 10.1186/s13071-019-3355-5 -
Molecular Microbiology Oct 2017Who wouldn't want to have a drug that is activated only in the target cell? Prodrugs that are metabolically triggered inside the pathogen but not in the host are an...
Who wouldn't want to have a drug that is activated only in the target cell? Prodrugs that are metabolically triggered inside the pathogen but not in the host are an attractive concept in antimicrobial chemotherapy. Of particular interest are bioreductive prodrugs such as nitro compounds or quinones that can initiate cytotoxic redox cascades and release active metabolites. The critical points for the selectivity of such molecules are, what is the source of the electrons that activate the prodrug, and which are the enzymes that catalyze the reduction? Meredith et al. conceive an elegant approach to answer these questions, making use of reverse genetics in Trypanosoma brucei. By overexpression of key reductase genes, they engineer trypanosomal indicator lines that are hypersensitive to particular bioreductive prodrugs and allow to discriminate between one-electron and two-electron transfer activation mechanisms. Indicator lines that are also defective in DNA repair further indicate whether the resultant metabolites interfere with the parasite's genome. This set of T. brucei indicator lines provides a tool for the deconvolution of the mechanisms of prodrug activation and drug action that will facilitate the rational development of bioreductive prodrugs for parasite chemotherapy.
Topics: Electrons; Humans; Oxidation-Reduction; Prodrugs; Quinones; Reverse Genetics; Trypanosoma brucei brucei
PubMed: 28833608
DOI: 10.1111/mmi.13773 -
Parasites & Vectors Feb 2022This review focuses on the most reliable and up-to-date methods for diagnosing trypanosomoses, a group of diseases of wild and domestic mammals, caused by trypanosomes,... (Review)
Review
This review focuses on the most reliable and up-to-date methods for diagnosing trypanosomoses, a group of diseases of wild and domestic mammals, caused by trypanosomes, parasitic zooflagellate protozoans mainly transmitted by insects. In Africa, the Americas and Asia, these diseases, which in some cases affect humans, result in significant illness in animals and cause major economic losses in livestock. A number of pathogens are described in this review, including several Salivarian trypanosomes, such as Trypanosoma brucei sspp. (among which are the agents of sleeping sickness, the human African trypanosomiasis [HAT]), Trypanosoma congolense and Trypanosoma vivax (causing "Nagana" or animal African trypanosomosis [AAT]), Trypanosoma evansi ("Surra") and Trypanosoma equiperdum ("Dourine"), and Trypanosoma cruzi, a Stercorarian trypanosome, etiological agent of the American trypanosomiasis (Chagas disease). Diagnostic methods for detecting zoonotic trypanosomes causing Chagas disease and HAT in animals, as well as a diagnostic method for detecting animal trypanosomes in humans (the so-called "atypical human infections by animal trypanosomes" [a-HT]), including T. evansi and Trypanosoma lewisi (a rat parasite), are also reviewed. Our goal is to present an integrated view of the various diagnostic methods and techniques, including those for: (i) parasite detection; (ii) DNA detection; and (iii) antibody detection. The discussion covers various other factors that need to be considered, such as the sensitivity and specificity of the various diagnostic methods, critical cross-reactions that may be expected among Trypanosomatidae, additional complementary information, such as clinical observations and epizootiological context, scale of study and logistic and cost constraints. The suitability of examining multiple specimens and samples using several techniques is discussed, as well as risks to technicians, in the context of specific geographical regions and settings. This overview also addresses the challenge of diagnosing mixed infections with different Trypanosoma species and/or kinetoplastid parasites. Improving and strengthening procedures for diagnosing animal trypanosomoses throughout the world will result in a better control of infections and will significantly impact on "One Health," by advancing and preserving animal, human and environmental health.
Topics: Animals; Dourine; Rats; Trypanosoma; Trypanosoma congolense; Trypanosoma vivax; Trypanosomiasis; Trypanosomiasis, African
PubMed: 35183235
DOI: 10.1186/s13071-022-05190-1 -
The Journal of Biological Chemistry Nov 2018Polyamines are polycationic organic amines that are required for all eukaryotic life, exemplified by the polyamine spermidine, which plays an essential role in... (Review)
Review
Polyamines are polycationic organic amines that are required for all eukaryotic life, exemplified by the polyamine spermidine, which plays an essential role in translation. They also play more specialized roles that differ across species, and their chemical versatility has been fully exploited during the evolution of protozoan pathogens. These eukaryotic pathogens, which cause some of the most globally widespread infectious diseases, have acquired species-specific polyamine-derived metabolites with essential cellular functions and have evolved unique mechanisms that regulate their core polyamine biosynthetic pathways. Many of these parasitic species have lost enzymes and or transporters from the polyamine metabolic pathway that are found in the human host. These pathway differences have prompted drug discovery efforts to target the parasite polyamine pathways, and indeed, the only clinically approved drug targeting the polyamine biosynthetic pathway is used to manage human African trypanosomiasis. This Minireview will primarily focus on polyamine metabolism and function in , , and species, which are the causative agents of human African trypanosomiasis (HAT) and Chagas disease, Leishmaniasis, and malaria, respectively. Aspects of polyamine metabolism across a diverse group of protozoan pathogens will also be explored.
Topics: Animals; Humans; Leishmania; Leishmaniasis; Malaria; Plasmodium; Polyamines; Trypanosoma; Trypanosomiasis, African
PubMed: 30333232
DOI: 10.1074/jbc.TM118.003342 -
Memorias Do Instituto Oswaldo Cruz 2022An increasing amount of research has led to the positioning of nucleoside diphosphate kinases (NDPK/NDK) as key metabolic enzymes among all organisms. They contribute to... (Review)
Review
BACKGROUND
An increasing amount of research has led to the positioning of nucleoside diphosphate kinases (NDPK/NDK) as key metabolic enzymes among all organisms. They contribute to the maintenance the intracellular di- and tri- phosphate nucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signal transduction and many other regulatory roles.
OBJETIVE
Examine in depth the NDPKs of trypanosomatid parasites responsible for devastating human diseases (e.g., Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) which deserve special attention.
METHODS
The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features, multifunctionality and suitability as molecular drug targets.
FINDINGS
Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that they would perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responses and gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractive pharmacological targets.
MAIN CONCLUSIONS
NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatid NDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.
Topics: Host-Parasite Interactions; Humans; Nucleoside-Diphosphate Kinase; Nucleotides; Trypanosoma brucei brucei; Trypanosoma cruzi
PubMed: 35170678
DOI: 10.1590/0074-02760210339 -
Trends in Parasitology Apr 2021Differentiation is a central aspect of the parasite life cycle and encompasses adaptation to both host and environment. If we accept that evolution cannot anticipate an... (Review)
Review
Differentiation is a central aspect of the parasite life cycle and encompasses adaptation to both host and environment. If we accept that evolution cannot anticipate an organism's needs as it enters a new environment, how do parasite differentiation pathways arise? The transition between vertebrate and insect stage African trypanosomes is probably one of the better studied and involves a cell-cycle arrested or 'stumpy' form that activates metabolic pathways advantageous to the parasite in the insect host. However, a range of stimuli and stress conditions can trigger similar changes, leading to formation of stumpy-like cellular states. We propose that the origin and optimisation of this differentiation program represents repurposing of a generic stress response to gain considerable gain-of-fitness associated with parasite transmission.
Topics: Biological Evolution; Cell Cycle; Life Cycle Stages; Stress, Physiological; Trypanosoma
PubMed: 33309505
DOI: 10.1016/j.pt.2020.11.003 -
Trends in Parasitology Nov 2022Trypanosomatid parasitic protozoa are divergent from opisthokont models and have evolved unique mechanisms to regulate their complex life cycles and to adapt to a range... (Review)
Review
Trypanosomatid parasitic protozoa are divergent from opisthokont models and have evolved unique mechanisms to regulate their complex life cycles and to adapt to a range of hosts. Understanding how these organisms respond, adapt, and persist in their different hosts could reveal optimal drug-control strategies. Protein kinases are fundamental to many biological processes such as cell cycle control, adaptation to stress, and cellular differentiation. Therefore, we have focused this review on the features and functions of protein kinases that distinguish trypanosomatid kinomes from other eukaryotes. We describe the latest research, highlighting similarities and differences between two groups of trypanosomatid parasites, Leishmania and African trypanosomes.
Topics: Animals; Leishmania; Life Cycle Stages; Protein Kinases; Trypanosoma
PubMed: 36075845
DOI: 10.1016/j.pt.2022.08.009 -
Molecules (Basel, Switzerland) Oct 2020Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus . In humans, this includes Chagas disease and African trypanosomiasis. There are few... (Review)
Review
Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus . In humans, this includes Chagas disease and African trypanosomiasis. There are few therapeutic options, and there is low efficacy to clinical treatment. Therefore, the search for new drugs for the trypanosomiasis is urgent. This review describes studies of the trypanocidal properties of essential oils, an important group of natural products widely found in several tropical countries. Seventy-seven plants were selected from literature for the trypanocidal activity of their essential oils. The main chemical constituents and mechanisms of action are also discussed. In vitro and in vivo experimental data show the therapeutic potential of these natural products for the treatment of infections caused by species of .
Topics: Animals; Chagas Disease; Humans; Oils, Volatile; Plant Extracts; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosoma cruzi; Trypanosomiasis, African
PubMed: 33036315
DOI: 10.3390/molecules25194568 -
Tropical Animal Health and Production Jun 2017Dourine is a venereal transmitted trypanosomosis causing a major health problem threatening equines worldwide. The origin and identification of Trypanosoma equiperdum... (Review)
Review
Dourine is a venereal transmitted trypanosomosis causing a major health problem threatening equines worldwide. The origin and identification of Trypanosoma equiperdum within the subgenus Trypanozoon is still a subject of debate. Unlike other trypanosomal infections, dourine is transmitted almost exclusively by coitus. Diagnosis of dourine has continued to be a challenge, due to limited knowledge about the parasite and host-parasite interaction following infection. The pathological lesions caused by the diseases are poorly described and are observed mainly in the reproductive organs, in the nervous system, and on the skin. Dourine has been neglected by research and current knowledge on the disease, and the parasite is very deficient despite its considerably high burden. This paper looks in to the challenges in identification of T. equiperdum and diagnosis techniques with the aim to update our current knowledge of the disease.
Topics: Animals; Dourine; Horse Diseases; Horses; Neglected Diseases; Trypanosoma
PubMed: 28439783
DOI: 10.1007/s11250-017-1280-1 -
Frontiers in Cellular and Infection... 2020and (Trypanosomatidae: Kinetoplastida) are parasitic protozoan causing Chagas disease, African Trypanosomiasis and Leishmaniases worldwide. They are vector borne... (Review)
Review
and (Trypanosomatidae: Kinetoplastida) are parasitic protozoan causing Chagas disease, African Trypanosomiasis and Leishmaniases worldwide. They are vector borne diseases transmitted by triatomine bugs, Tsetse fly, and sand flies, respectively. Those diseases cause enormous economic losses and morbidity affecting not only rural and poverty areas but are also spreading to urban areas. During the parasite-host interaction, those organisms release extracellular vesicles (EVs) that are crucial for the immunomodulatory events triggered by the parasites. EVs are involved in cell-cell communication and can act as important pro-inflammatory mediators. Therefore, interface between EVs and host immune responses are crucial for the immunopathological events that those diseases exhibit. Additionally, EVs from these organisms have a role in the invertebrate hosts digestive tracts prior to parasite transmission. This review summarizes the available data on how EVs from those medically important trypanosomatids affect their interaction with vertebrate and invertebrate hosts.
Topics: Animals; Cell Communication; Chagas Disease; Extracellular Vesicles; Trypanosoma brucei brucei; Trypanosoma cruzi
PubMed: 33381465
DOI: 10.3389/fcimb.2020.602502