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1.
Parasit Vectors ; 17(1): 152, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519971

RESUMO

BACKGROUND: In the family Trypanosomatidae, the genus Trypanosoma contains protozoan parasites that infect a diverse range of hosts, including humans, domestic animals, and wildlife. Wild rodents, as natural reservoir hosts of various pathogens, play an important role in the evolution and emergence of Trypanosomatidae. To date, no reports are available on the trypanosomatid infection of pikas (Lagomorpha: Ochotonidae). METHODS: In this study, Mongolian pikas and their fleas were sampled at the China-Mongolia border, northwestern China. The samples were analyzed with polymerase chain reaction (PCR) and sequencing for the presence of Trypanosomatidae on the basis of both the 18S ribosomal RNA (18S rRNA) gene and the glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) gene. The morphology of trypomastigotes was also observed in peripheral blood smears by microscopy. RESULTS: Molecular and phylogenetic analyses revealed a new genotype of the Trypanosoma lewisi clade that was found both in pika blood and flea samples. This genotype, which probably represents a new species, was provisionally designated as "Trypanosoma sp. pika". In addition, a novel genotype belonging to the genus Blechomonas of Trypanosomatidae was detected in fleas. On the basis of its molecular and phylogenetic properties, this genotype was named Blechomonas luni-like, because it was shown to be the closest related to B. luni compared with other flea-associated trypanosomatids. CONCLUSIONS: To the best of our knowledge, this is the first study to report any trypanosomatid species in Mongolian pikas and their fleas. Further studies are needed to investigate the epidemiology of these protozoan parasites, as well as to evaluate their pathogenicity for humans or domestic animals.


Assuntos
Lagomorpha , Sifonápteros , Trypanosoma , Trypanosomatina , Animais , Humanos , Lagomorpha/parasitologia , Sifonápteros/parasitologia , Filogenia , China/epidemiologia , Trypanosoma/genética , Trypanosomatina/genética , Animais Domésticos , Gerbillinae
2.
Parasite ; 31: 15, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38520091

RESUMO

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. Furthermore, the understanding of Tbg2's potential to infect tsetse flies and mammalian hosts is limited. In this study, 165 Glossina palpalis gambiensis flies were experimentally infected with procyclic Tbg2 parasites. It was found that 35 days post-infection, 43 flies out of the 80 still alive were found to be Tbg2 PCR-positive in the saliva. These flies were able to infect 3 out of the 4 mice used for blood-feeding. Dissection revealed that only six flies in fact carried mature infections in their midguts and salivary glands. Importantly, a single fly with a mature infection was sufficient to infect a mammalian host. This Tbg2 transmission success confirms that Tbg2 strains can establish in tsetse flies and infect mammalian hosts. This study describes an effective in vivo protocol for transforming Tbg2 from procyclic to bloodstream form, reproducing the complete Tbg2 cycle from G. p. gambiensis to mice. These findings provide valuable insights into Tbg2's host infectivity, and will facilitate further research on mechanisms of human serum resistance.


Title: Cycle de vie expérimental in vivo de Trypanosoma brucei gambiense groupe 2 : de la forme procyclique à la forme sanguicole. Abstract: Trypanosoma brucei gambiense (Tbg) groupe 2 est un sous-groupe de trypanosomes capables d'infecter l'Homme, présent en Afrique de l'Ouest et en Afrique centrale. Contrairement aux autres agents responsables de la maladie du sommeil, tels que Tbg groupe 1 et Trypanosoma brucei rhodesiense, Tbg2 ne présente pas les marqueurs moléculaires habituellement associés à la résistance au sérum humain. Seules trente-six souches de Tbg2 ont été répertoriées, limitant considérablement les recherches sur ce sous-groupe malgré sa nature zoonotique. Certaines de ces souches ne sont disponibles que sous leur forme procyclique, ce qui freine la réalisation des tests de résistance au sérum humain et les études mécanistiques. De plus, la compréhension du potentiel de Tbg2 à infecter les glossines et les hôtes mammifères est limitée. Dans cette étude, 165 glossines Glossina palpalis gambiensis ont été infectées expérimentalement par des parasites Tbg2 sous leur forme procyclique. Trente-cinq jours après l'infection, 43 des 80 glossines encore en vie se sont révélées positives à Tbg2 en PCR sur leur salive. Ces glossines ont réussi à infecter trois des quatre souris utilisées pour leur repas de sang. La dissection des glossines a révélé que seules six d'entre elles étaient réellement porteuses d'infections matures dans leur intestin et leurs glandes salivaires. Il est important de noter qu'une seule glossine porteuse d'une infection mature a suffi pour infecter un hôte mammifère. Ce succès de transmission de Tbg2 confirme que les souches de Tbg2 peuvent s'établir dans les glossines et infecter des hôtes mammifères. Cette étude décrit un protocole in vivo pour transformer la forme procyclique de Tbg2 en forme sanguicole, en reproduisant le cycle complet de Tbg2 de G. p. gambiensis à la souris. Ces résultats fournissent des informations précieuses sur le potentiel infectieux de Tbg2 et faciliteront la recherche sur les mécanismes de résistance au sérum humain des souches.


Assuntos
Trypanosoma brucei brucei , Trypanosoma , Tripanossomíase Africana , Moscas Tsé-Tsé , Animais , Humanos , Camundongos , Trypanosoma brucei gambiense , Tripanossomíase Africana/parasitologia , Moscas Tsé-Tsé/parasitologia , Estágios do Ciclo de Vida , Mamíferos
3.
Sci Rep ; 14(1): 6972, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521853

RESUMO

This study compared effects of diminazene aceturate (berenil), commonly used to treat domestic animals infected with Trypanosoma evansi, with the hemolymph of Sarcophaga argyostoma larva. The hemolymph may be acting as a possible natural alternative to berenil, based on immunomodulation mediated inflammatory response. Inflammatory mediators and histopathological changes in liver, kidney, and spleen of albino mice experimentally infected with T. evansi were studied. Mice were divided into five groups: G1, uninfected, untreated (negative control); G2, T. evansi infected (positive control); G3, infected and treated with berenil; G4, infected and treated with hemolymph; G5, infected and treated with hemolymph 3 days before infection (prophylactic group). Animals in (G4) and (G5) exhibited a significant overall reduction in serum levels of IFN-γ. However, the reduction in TNF-α and IL-6 levels was more limited compared to (G2) and (G3). Notably, an elevation in IL-10 levels was observed compared to animals in other groups. Furthermore, the groups treated with hemolymph demonstrated an alleviation of T. evansi infection in contrast to the other groups. This study highlights that the administration of Sarcophaga argyostoma larval hemolymph at a dosage of 0.5 ml/kg significantly inhibited T. evansi organisms in vivo, showcasing a pronounced trypanocidal effect.


Assuntos
Diminazena/análogos & derivados , Sarcofagídeos , Tripanossomicidas , Trypanosoma , Camundongos , Animais , Tripanossomicidas/farmacologia , Hemolinfa
4.
Parasitol Res ; 123(3): 166, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506929

RESUMO

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. Therefore, in the present study, the presence of a plasma membrane Ca2+-channel in T. equiperdum (TeCC), activated by sphingosine and inhibited by verapamil, is described. The TeCC was cloned and analyzed using bioinformatic resources, which confirmed the presence of several domains, motifs, and a topology similar to the Ca2+ channels found in higher eukaryotes. Biochemical and confocal microscopy assays using antibodies raised against an internal region of human L-type Ca2+ channels indicate the presence of a protein with similar predicted molar mass to the sequence analyzed, located at the plasma membrane of T. equiperdum. Physiological assays based on Fura-2 signals and Mn2+ quenching performed on whole parasites showed a unidirectional Ca2+ entry, which is activated by sphingosine and blocked by verapamil, with the distinctive feature of insensitivity to nifedipine and Bay K 8644. This suggests a second Ca2+ entry for T. equiperdum, different from the store-operated Ca2+ entry (SOCE) previously described. Moreover, the evidence presented here for the TeCC indicates molecular and pharmacological differences with their mammal counterparts, which deserve further studies to evaluate the potential of this channel as a drug target.


Assuntos
Esfingosina , Trypanosoma , Animais , Humanos , Esfingosina/farmacologia , Verapamil/farmacologia , Membrana Celular/metabolismo , Cálcio/metabolismo , Mamíferos
5.
Front Cell Infect Microbiol ; 14: 1274506, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510966

RESUMO

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. Using yeast two-hybrid analysis, we demonstrate that TbPEX1 can bind to TbPEX6. Endogenously tagged TbPEX1 localizes to glycosomes in the T. brucei parasites. Depletion of PEX1 gene expression by RNA interference causes lethality to the bloodstream form trypanosomes, due to a partial mislocalization of glycosomal enzymes to the cytosol and ATP depletion. TbPEX1 RNAi leads to a selective proteasomal degradation of both matrix protein import receptors TbPEX5 and TbPEX7. Unlike in yeast, PEX1 depletion did not result in an accumulation of ubiquitinated TbPEX5 in trypanosomes. As PEX1 turned out to be essential for trypanosomatid parasites, it could provide a suitable drug target for parasitic diseases. The results also suggest that these parasites possess a highly efficient quality control mechanism that exports the import receptors from glycosomes to the cytosol in the absence of a functional TbPEX1-TbPEX6 complex.


Assuntos
Parasitos , Proteínas de Saccharomyces cerevisiae , Trypanosoma , Animais , Parasitos/metabolismo , Saccharomyces cerevisiae/metabolismo , Peroxissomos/genética , Peroxissomos/metabolismo , Microcorpos , ATPases Associadas a Diversas Atividades Celulares/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
6.
Comp Immunol Microbiol Infect Dis ; 107: 102156, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38457963

RESUMO

Virulent species or strains of hematophagous borne pathogens such as Anaplasma spp., Babesia spp., Theileria spp., and Trypanosoma spp., are lethal to susceptible animals or reduce their productivity on a global scale. Nonetheless, efforts to diagnose the causative agents and assess the genotypic profiles as well as quantify the parasite burden of aforementioned parasites across seasons remain limited. Therefore, the present investigation sought to elucidate the genotypic composition of Anaplasma spp., Babesia spp., Theileria spp., and Trypanosoma spp. The findings revealed heightened infection rates during the summer, manifesting a correlation between Trypanosoma spp. infection and seasonal fluctuations. Among the identified pathogens, Anaplasma marginale emerged as the most dominant species, while the occurrence of Anaplasma platys in Thai cattle was confirmed via the sequencing of the groEL gene. Moreover, the study successfully identified two lineages of Trypanosoma theileri. The findings of this investigation offer valuable insights that can inform the development of preventive strategies for vector-borne diseases, such as considering the appropriate use of insect repellent, mosquito or insect nets, or eliminating breeding places for insects in each season.


Assuntos
Anaplasmose , Artrópodes , Babesia , Doenças dos Bovinos , Parasitos , Theileria , Doenças Transmitidas por Carrapatos , Trypanosoma , Animais , Bovinos , Estações do Ano , Tailândia/epidemiologia , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/parasitologia , Anaplasma/genética , Babesia/genética , Theileria/genética , Trypanosoma/genética , Anaplasmose/epidemiologia , Doenças Transmitidas por Carrapatos/veterinária
7.
Onderstepoort J Vet Res ; 91(1): e1-e6, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38426744

RESUMO

Trypanosomosis is a disease complex which affects both humans and animals in sub-Saharan Africa, transmitted by the tsetse fly and distributed within the tsetse belt of Africa. But some trypanosome species, for example, Trypanosoma brucei evansi, T. vivax, T. theileri and T. b. equiperdum are endemic outside the tsetse belt of Africa transmitted by biting flies, for example, Tabanus and Stomoxys, or venereal transmission, respectively. Trypanocidal drugs remain the principal method of animal trypanosomosis control in most African countries. However, there is a growing concern that their effectiveness may be severely curtailed by widespread drug resistance. A minimum number of six male cattle calves were recruited for the study. They were randomly grouped into two (T. vivax and T. congolense groups) of three calves each. One calf per group served as a control while two calves were treatment group. They were inoculated with 105 cells/mL parasites in phosphate buffered solution (PBS) in 2 mL. When parasitaemia reached 1 × 107.8 cells/mL trypanosomes per mL in calves, treatment was instituted with 20 mL (25 mg/kg in 100 kg calf) ascofuranone (AF) for treatment calves, while the control ones were administered a placebo (20 mL PBS) intramuscularly. This study revealed that T. vivax was successfully cleared by AF but the T. congolense group was not cleared effectively.Contribution: There is an urgent need to develop new drugs which this study sought to address. It is suggested that the AF compound can be developed further to be a sanative drug for T. vivax in non-tsetse infested areas like South Americas.


Assuntos
Sesquiterpenos , Tripanossomicidas , Tripanossomíase Africana , Animais , Bovinos , Masculino , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Trypanosoma , Tripanossomíase Africana/tratamento farmacológico , Tripanossomíase Africana/veterinária , Tripanossomíase Africana/epidemiologia , Moscas Tsé-Tsé/parasitologia
8.
Parasitol Res ; 123(3): 156, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457016

RESUMO

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. Subsequently, the sequence-structure phylogeny is employed to classify new trypanosome sequences discovered in wild birds, placing them within the Ornithotrypanum subgenus. This marks the first identification of Ornithotrypanum in Neotropical birds, contributing to the understanding of the distribution and ecological adaptation of avian trypanosomes. Beyond taxonomy, this study broadens our comprehension of the ecological implications of avian trypanosomes in the Neotropics, emphasizing the need for continued research in this field. These findings underscore the importance of alternative classification methods, which are essential to unravel the complex interactions between parasites, wildlife hosts, and their ecosystems.


Assuntos
Aves Canoras , Trypanosoma , Animais , Humanos , Ecossistema , RNA Ribossômico 18S/genética , Trypanosoma/genética , Filogenia , Animais Selvagens/genética
9.
Parasit Vectors ; 17(1): 52, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308365

RESUMO

BACKGROUND: Tsetse flies (Glossina spp.) are the definitive biological vectors of African trypanosomes in humans and animals. Controlling this vector is the most promising method of preventing trypanosome transmission. This requires a comprehensive understanding of tsetse biology and host preference to inform targeted design and management strategies, such as the use of olfaction and visual cues in tsetse traps. No current review exists on host preference and blood meal analyses of tsetse flies. METHODS: This review presents a meta-analysis of tsetse fly blood meal sources and the methodologies used to identify animal hosts from 1956 to August 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRIMA-ScR) was applied. This focused on tsetse-endemic countries, blood meal analysis methodologies and the blood meal hosts identified. The articles were retrieved and screened from databases using predetermined eligibility criteria. RESULTS: Only 49/393 of the articles retrieved matched the inclusion criteria. Glossina's main hosts in the wild included the bushbuck, buffalo, elephant, warthog, bushpig and hippopotamus. Pigs, livestock and humans were key hosts at the domestic interface. The least studied species included Glossina fuscipleuris, G. fusca, G. medicorum, G. tabaniformis and G. austeni. In the absence of preferred hosts, Glossina fed opportunistically on a variety of hosts. Precipitin, haemagglutination, disc diffusion, complement fixation, ELISA and PCR-based assays were used to evaluate blood meals. Cytochrome b (Cyt b) was the main target gene in PCR to identify the vertebrate hosts. CONCLUSIONS: Tsetse blood meal sources have likely expanded because of ecological changes that could have rendered preferred hosts unavailable. The major approaches for analysing tsetse fly blood meal hosts targeted Cyt b gene for species identification by Sanger sequencing. However, small-fragment DNAs, such as the mammalian 12S and 16S rRNA genes, along with second- and third-generation sequencing techniques, could increase sensitivity for host identification in multiple host feeders that Sanger sequencing may misidentify as "noise". This review of tsetse fly blood meal sources and approaches to host identification could inform strategies for tsetse control.


Assuntos
Trypanosoma , Tripanossomíase Africana , Moscas Tsé-Tsé , Animais , Humanos , Citocromos b , Mamíferos/genética , RNA Ribossômico 16S , Suínos , Trypanosoma/genética , Moscas Tsé-Tsé/genética
10.
Acta Trop ; 252: 107148, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354996

RESUMO

Trypanosoma evansi is a flagellate protozoan that infects a wide range of hosts, especially horses. Clinically, the infection is characterized by rapid weight loss, anemia and mobility disorders. This study evaluated the efficacy of treatment gallium maltolate (GaM) in rats infected with T. evansi in the acute and chronic phases of the disease and its influence on the enzyme and blood parameters. 48 animals (Rattus norvegicus) were divided into 8 groups (A-H) of 6 animals each, namely: A: (negative control) uninfected; B: acutely infected positive control; C: chronically infected positive control; D: acutely infected, treated with GaM for 7 days post infection (p.i.); E: acutely infected treated with GaM for 3 days before infection (b.i) and 7 days p.i.; F: chronically infected, treated with GaM for 7 days p.i.; G: chronically infected, treated with GaM for 3 days b.i. and 7 days p.i.; and H: uninfected treated with GaM for 10 days. Acute infected animals (B, D and E) had a progressive increase in parasitemia and were died or euthanized before completing treatment days (5th days p.i.) as they had high parasitemia (over 100 field trypanosomes in the blood smear). Thus, it can be concluded that GaM was not effective against an acute infection. In untreated chronically infected animals (C) the parasitemia also increased progressively and they were euthanized on the 7th day p.i.. The chronically infected and treated animals (F and G) showed low parasitemia and after treatment became negative, showing no trypanosomes in the bloodstream until the 50th day of the experiment. Thus, we conclude that GaM was effective against chronic infections. In uninfected and treated animals (H) hematological, biochemical and enzymatic parameters had no significant changes when compared to the negative control group (A) demonstrating the low toxicity of GaM.


Assuntos
Anemia , Compostos Organometálicos , Pironas , Trypanosoma , Tripanossomíase , Camundongos , Ratos , Cavalos , Animais , Tripanossomíase/tratamento farmacológico , Tripanossomíase/veterinária , Parasitemia/tratamento farmacológico
11.
Exp Parasitol ; 259: 108711, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38355002

RESUMO

Animal African trypanosomosis (AAT) is a disease caused by Trypanosoma brucei brucei, T. vivax, T. evansi and T. congolense which are mainly transmitted by tsetse flies (maybe the family/genus scientific name for the tsetse flies here?). Synthetic trypanocidal drugs are used to control AAT but have reduced efficacy due to emergence of drug resistant trypanosomes. Therefore, there is a need for the continued development of new safe and effective drugs. The aim of this study was to evaluate the in vitro anti-trypanosomal activity of novel nitrofurantoin compounds against trypanosomes (Trypanosoma brucei brucei, T. evansi and T. congolense) causing AAT. This study assessed previously synthesized nineteen nitrofurantoin-triazole (NFT-TZ) hybrids against animal trypanosomes and evaluated their cytotoxicity using Madin-Darby bovine kidney cells. The n-alkyl sub-series hybrids, 8 (IC50 0.09 ± 0.02 µM; SI 686.45) and 9 (IC50 0.07 ± 0.04 µM; SI 849.31) had the highest anti-trypanosomal activity against T. b. brucei. On the contrary, the nonyl 6 (IC50 0.12 ± 0.06 µM; SI 504.57) and nitrobenzyl 18 (IC50 0.11 ± 0.03 µM; SI 211.07) displayed the highest trypanocidal activity against T. evansi. The nonyl hybrid 6 (IC50 0.02 ± 0.01 µM; SI 6328.76) was also detected alongside the undecyl 8 (IC50 0.02 ± 0.01 µM; SI 3454.36) and 3-bromobenzyl 19 (IC50 0.02 ± 0.01 µM; SI 2360.41) as the most potent hybrids against T. congolense. These hybrids had weak toxicity effects on the mammalian cells and highly selective submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further in vivo investigation.


Assuntos
Trypanosoma brucei brucei , Trypanosoma congolense , Trypanosoma , Tripanossomíase Africana , Moscas Tsé-Tsé , Animais , Bovinos , Nitrofurantoína/farmacologia , Tripanossomíase Africana/tratamento farmacológico , Tripanossomíase Africana/veterinária , Tripanossomíase Africana/parasitologia , Moscas Tsé-Tsé/parasitologia , Mamíferos
12.
Sci Rep ; 14(1): 4158, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378867

RESUMO

Animal African trypanosomiasis (AAT) is a significant food security and economic burden in sub-Saharan Africa. Current AAT empirical and immunodiagnostic surveillance tools suffer from poor sensitivity and specificity, with blood sampling requiring animal restraint and trained personnel. Faecal sampling could increase sampling accessibility, scale, and species range. Therefore, this study assessed feasibility of detecting Trypanosoma DNA in the faeces of experimentally-infected cattle. Holstein-Friesian calves were inoculated with Trypanosoma brucei brucei AnTat 1.1 (n = 5) or T. congolense Savannah IL3000 (n = 6) in separate studies. Faecal and blood samples were collected concurrently over 10 weeks and screened using species-specific PCR and qPCR assays. T. brucei DNA was detected in 85% of post-inoculation (PI) faecal samples (n = 114/134) by qPCR and 50% by PCR between 4 and 66 days PI. However, T. congolense DNA was detected in just 3.4% (n = 5/145) of PI faecal samples by qPCR, and none by PCR. These results confirm the ability to consistently detect T. brucei DNA, but not T. congolense DNA, in infected cattle faeces. This disparity may derive from the differences in Trypanosoma species tissue distribution and/or extravasation. Therefore, whilst faeces are a promising substrate to screen for T. brucei infection, blood sampling is required to detect T. congolense in cattle.


Assuntos
Trypanosoma brucei brucei , Trypanosoma congolense , Trypanosoma , Tripanossomíase Africana , Humanos , Bovinos , Animais , Trypanosoma brucei brucei/genética , Trypanosoma congolense/genética , Tripanossomíase Africana/diagnóstico , Tripanossomíase Africana/veterinária , Tripanossomíase Africana/epidemiologia , Trypanosoma/genética , DNA , Fezes
13.
Eur J Med Chem ; 268: 116162, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394930

RESUMO

Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease with current treatments marred by severe side effects or delivery issues. To identify novel classes of compounds for the treatment of HAT, high throughput screening (HTS) had previously been conducted on bloodstream forms of T. b. brucei, a model organism closely related to the human pathogens T. b. gambiense and T. b. rhodesiense. This HTS had identified a number of structural classes with potent bioactivity against T. b. brucei (IC50 ≤ 10 µM) with selectivity over mammalian cell-lines (selectivity index of ≥10). One of the confirmed hits was an aroyl guanidine derivative. Deemed to be chemically tractable with attractive physicochemical properties, here we explore this class further to develop the SAR landscape. We also report the influence of the elucidated SAR on parasite metabolism, to gain insight into possible modes of action of this class. Of note, two sub-classes of analogues were identified that generated opposing metabolic responses involving disrupted energy metabolism. This knowledge may guide the future design of more potent inhibitors, while retaining the desirable physicochemical properties and an excellent selectivity profile of the current compound class.


Assuntos
Parasitos , Tripanossomicidas , Trypanosoma brucei brucei , Trypanosoma , Tripanossomíase Africana , Animais , Humanos , Tripanossomicidas/química , Trypanosoma brucei rhodesiense , Guanidina/farmacologia , Tripanossomíase Africana/tratamento farmacológico , Tripanossomíase Africana/parasitologia , Guanidinas/farmacologia , Metabolismo Energético , Mamíferos
14.
Parasitol Res ; 123(1): 88, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38190005

RESUMO

Trypanosoma evansi is a widespread and neglected zoonotic parasite that affects domestic and wild animals, causing a disease commonly known as "surra." The Brazilian Pantanal wetland is recognized as an enzootic area for this protozoan, yet recognizing the importance of reservoir hosts also in order to prevent zoonotic outbreaks. This study aimed to assess the occurrence of T. evansi in jaguars (Panthera onca) from the Brazilian Pantanal wetland and explore associated clinical and hematological manifestations. A total of 42 animals were screened by PCR and sequenced for species identification when positive. Trypanosoma evansi was detected in six free-ranging jaguars (six positive animals of 42 captures and 16 recaptures), representing the first molecular evidence of such infection in this animal species. Our findings suggest that jaguars may act as reservoir hosts of T. evansi in the Brazilian Pantanal wetland. The better understanding of the role of wildlife in the epidemiology of T. evansi is also of importance to future reintroduction and translocation programs toward wildlife conservation efforts.


Assuntos
Panthera , Trypanosoma , Animais , Brasil/epidemiologia , Áreas Alagadas , Trypanosoma/genética , Animais Selvagens
15.
Vet Parasitol Reg Stud Reports ; 47: 100970, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38199676

RESUMO

Due to the proximity of humans to the countryside and the progressive increase in populations of invasive species, such as wild boars (Sus scrofa), the risk of disease spread is also exacerbated, some of which are zoonoses caused by protozoa. In the present study, 75 tissue/organ samples from 25 wild boars obtained from authorized hunting in the northern region of Rio Grande do Sul were evaluated to investigate the presence of Trypanosoma spp. using conventional PCR with specific primers and amplification of the ITS1 region for Leishmania spp. detection and species differentiation, multiplex PCR with kDNA minicircle amplification was performed. Trypanosoma spp. DNA was detected in 11 out of 25 hearts, representing 44% of the culled animals. Regarding the detection of Leishmania DNA, L. infantum was detected in one spleen sample, accounting for 4%, and L. amazonensis in one liver sample from the same animal, also representing 4% (1/25) of the samples. It is important to note that this wild boar, with detection for both L. amazonensis and L. infantum, also had Trypanosoma spp. DNA detected in a heart sample, indicating the potential of this species to have multiple infections with these agents. Furthermore, this is the first reported case of multiple infection in a wild boar with these agents. Therefore, the results obtained reinforce the risk posed by invasive species, especially wild boars, as potential sources of infectious agent dissemination and their role as possible reservoirs for numerous diseases.


Assuntos
Leishmania , Trypanosoma , Animais , Humanos , Suínos , Leishmania/genética , DNA , Espécies Introduzidas , Trypanosoma/genética , Sus scrofa
16.
J Vet Med Sci ; 86(1): 35-38, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38008465

RESUMO

Goat production is an important source of livelihood and food. Goats may serve as reservoir of surra affecting livestock production. Here, forty-two free-roaming goats from Cavite, Philippines were screened using two primer sets, Trypanosoma brucei minisatellite chromosome for initial detection and the internal transcribed spacer 1 (ITS-1) to determine phylogeny. Initial PCR detection showed that 19/42 (45%) goats were positive, much higher than the rate previously reported in goats from Cebu (34%). The infectivity rate was higher in male (56%) than in female (42%) and the rate was higher in young ≤1 year old (100%) than in adult >1 year old (43%). Phylogenetic analysis of the ITS-1 sequences between T. evansi goat samples and other isolates indicate potential interspecies transmission.


Assuntos
Doenças das Cabras , Trypanosoma , Tripanossomíase , Feminino , Masculino , Animais , Cabras , Filipinas/epidemiologia , Filogenia , DNA de Protozoário/genética , Trypanosoma/genética , Tripanossomíase/epidemiologia , Tripanossomíase/veterinária , Doenças das Cabras/epidemiologia , Doenças das Cabras/diagnóstico
17.
mSphere ; 9(1): e0036323, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38126788

RESUMO

Nucleoside analogs have been used extensively as anti-infective agents, particularly against viral infections, and have long been considered promising anti-parasitic agents. These pro-drugs are metabolized by host-cell, viral, or parasite enzymes prior to incorporation into DNA, thereby inhibiting DNA replication. Here, we report genes that sensitize African trypanosomes to nucleoside analogs, including the guanosine analog, ganciclovir. We applied ganciclovir selective pressure to a trypanosome genome-wide knockdown library, which yielded nucleoside mono- and diphosphate kinases as hits, validating the approach. The two most dominant hits to emerge, however, were Tb927.6.2800 and Tb927.6.2900, which both encode nuclear proteins; the latter of which is HD82, a SAMHD1-related protein and a putative dNTP triphosphohydrolase. We independently confirmed that HD82, which is conserved among the trypanosomatids, can sensitize Trypanosoma brucei to ganciclovir. Since ganciclovir activity depends upon phosphorylation by ectopically expressed viral thymidine kinase, we also tested the adenosine analog, ara-A, that may be fully phosphorylated by native T. brucei kinase(s). Both Tb927.6.2800 and HD82 knockdowns were resistant to this analog. Tb927.6.2800 knockdown increased sensitivity to hydroxyurea, while dNTP analysis indicated that HD82 is indeed a triphosphohydrolase with dATP as the preferred substrate. Our results provide insights into nucleoside/nucleotide metabolism and nucleoside analog metabolism and resistance in trypanosomatids. We suggest that the product of 6.2800 sensitizes cells to purine analogs through DNA repair, while HD82 does so by reducing the native purine pool.IMPORTANCEThere is substantial interest in developing nucleoside analogs as anti-parasitic agents. We used genome-scale genetic screening and discovered two proteins linked to purine analog resistance in African trypanosomes. Our screens also identified two nucleoside kinases required for pro-drug activation, further validating the approach. The top novel hit, HD82, is related to SAMHD1, a mammalian nuclear viral restriction factor. We validated HD82 and localized the protein to the trypanosome nucleus. HD82 appears to sensitize trypanosomes to nucleoside analogs by reducing native pools of nucleotides, providing insights into both nucleoside/nucleotide metabolism and nucleoside analog resistance in trypanosomatids.


Assuntos
Nucleosídeos , Trypanosoma , Animais , Nucleosídeos/metabolismo , Proteína 1 com Domínio SAM e Domínio HD , Trypanosoma/metabolismo , Purinas/metabolismo , Nucleotídeos/metabolismo , Ganciclovir/metabolismo , Mamíferos
18.
Acta Trop ; 251: 107113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38157924

RESUMO

Bats are one of the groups of mammals with the highest number of associated Trypanosoma taxa. There are 50 Trypanosoma species and genotypes infecting more than 75 species of bats across five continents. However, in Mexico, the inventory of species of the genus Trypanosoma associated with bats is limited to only two species (Trypanosoma vespertilionis and Trypanosoma cruzi) even though 140 species of bats inhabit this country. Specifically, 91 bat species have been recorded in the state of Veracruz, but records of trypanosomatids associated with this mammalian group are absent. Due to the complex Trypanosoma-bat relationship, the high diversity of bat species in Veracruz, as well as the lack of records of trypanosomatids associated with bats for this state, the aim of this work was to analyze the diversity of species of the genus Trypanosoma and their presence from a bat community in the central area of the state of Veracruz, Mexico. During the period of January to August 2022 in the Tequecholapa Environmental Management Unit where bats were collected using mist nets and blood samples were obtained from their thumbs. We extracted genetic material and amplified a fragment of 800 bp of the 18S ribosomal gene of the genus Trypanosoma by conventional PCR. The positive amplicons were sequenced, and phylogenetic reconstruction was performed to identify the parasite species. A total of 285 bats (149♀, 136♂) belonging to 13 species from 10 genera and a single family (Phyllostomidae) were collected. Twenty-three specimens from six species tested positive for the presence of Trypanosoma dionisii, Trypanosoma sp. Neobat 4, and a potential novelty species provisionally named as Trypanosoma sp. Neobat 6. The results of the present work increase the number of species of the genus Trypanosoma infecting bats in Mexico and in the Neotropical region.


Assuntos
Quirópteros , Trypanosoma cruzi , Trypanosoma , Animais , Quirópteros/parasitologia , Filogenia , México , Trypanosoma/genética , Trypanosoma cruzi/genética , Sequência de Bases
19.
Parasitol Res ; 123(1): 2, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38047956

RESUMO

Trypanosoma evansi infects domestic animals, causing a debilitating and occasionally fatal disease. The disease leads to significant economic losses to farmers and poses a substantial impediment to the growth of livestock production in developing nations, including India. Considering the challenges associated with managing this infection, there is an urgent need to enhance our understanding of the molecular and genetic diversity of T. evansi. Therefore, this study was planned to analyze the genetic diversity of T. evansi using available internal transcribed spacer-1 (ITS-1) gene sequences from India and compare them with sequences from around the globe. Blood samples used in this study were collected from naturally infected animals including dogs, cattle, and buffaloes in the Indian state of Madhya Pradesh. Using the ITS-1 gene, we amplified a 540 base pairs (bp) segment using polymerase chain reaction (PCR), sequenced it, and identified intra-specific variations. Phylogenetic analysis of 90 sequences, including 27 from India, revealed three distinct clusters with high bootstrap support values. A haplotype network analysis identified 34 haplotypes, with H7 being the most prevalent, indicating a complex evolutionary history involving multiple countries. The genetic analysis of the Indian population revealed distinct characteristics. Despite low nucleotide diversity, there was high haplotype diversity in comparison to other populations. Tajima's D, Fu and Li's D, and Fu and Li's F exhibited non-significant negative values, indicating potential stability. Additionally, the slightly positive values in Fu's Fs, Raggedness (r), and Ramos-Onsins and Rozas (R2) statistics suggested a lack of recent significant selective pressures or population expansions. Furthermore, the presence of genetic differentiation and gene flow among T. evansi populations highlighted ongoing evolutionary processes. These findings collectively depicted a complex genetic landscape, suggesting both stability and ongoing evolutionary dynamics within the Indian population of T. evansi. The findings of this study are important for understanding the evolutionary history and population dynamics of T. evansi, and they may help us develop effective control strategies.


Assuntos
Bison , Trypanosoma , Animais , Bovinos , Cães , Animais Domésticos , Filogenia , Trypanosoma/genética , Gado , Búfalos , Variação Genética
20.
Parasitol Res ; 123(1): 10, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38057596

RESUMO

Fish trypanosomiasis is a common blood parasitic disease transmitted by aquatic invertebrates, such as leeches. This study aims to shed light on the cytotoxicity of Trypanosoma sp. on erythrocytes and its impacts on the innate immune response (serum lysozyme activity, nitric oxide production, phagocytic activity, serum total protein, and globulin) in wild African catfish, Clarias gariepinus. One hundred catfish were examined using blood smears stained with Giemsa and confirmed with PCR. The prevalence of infection was found to be 10% by microscope detection and 15% by PCR. The morphological identification of Trypanosoma as Trypanosoma mukasai was determined. Additionally, this study included previously undescribed features of Trypanosoma, such as the width of the anterior and posterior body, the length of the posterior pale region, and the number of folds. Various alterations in erythrocytes were observed, totaling 54.57%. Nuclear abnormalities, including fragmented nuclei, eccentric nuclei, and micronuclei, were also reported. Infected fish showed a reduction in serum total protein and globulin levels, while nitric oxide production, lysozyme activity, and phagocytic activity exhibited a significant increase compared to non-infected fish. We believe that our findings will contribute valuable data to the morphological and molecular identification of Trypanosoma sp. in African catfish, as well as their cytotoxic impact.


Assuntos
Peixes-Gato , Globulinas , Trypanosoma , Animais , Peixes-Gato/parasitologia , Muramidase , Óxido Nítrico
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