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At least 19 recordsLinked to original sources
PubMed2026

De Novo Assembly of the Trypanosoma congolense Genome Reveals an Organization Influenced by Antigenic Variation but Distinct from Trypanosoma brucei.

Antigenic variation allows pathogens to evade mammalian adaptive immunity through the continuous change in exposed antigens. In African trypanosomes, antigenic variation involves changes in expressed Variant Surface Glycoproteins (VSGs). Understanding of VSG expression control and change amongst African trypanosomes is most advanced in Trypanosoma brucei. In the important animal trypanosome, Trypanosoma congolense, incomplete genome assembly has held back understanding of the mechanics of antigenic variation. Here, we have used long-read DNA sequencing and Hi-C DNA interaction analysis to provide a telomere-to-telomere assembly of the T. congolense genome. This assembly reveals a genome comprising 12 diploid chromosomes, one tetraploid chromosome, and more than 100 small chromosomes. With this assembly we reveal several features of VSG organization and expression that differ from T. brucei. The majority of the T. congolense VSG archive, estimated at ∼1,500 genes, localizes to subtelomeres in 12 of the 13 large chromosomes, but these loci are notably smaller than are found in T. brucei. Furthermore, transcriptome analysis suggests expression of VSGs across the T. congolense subtelomeres, which are not separated within the nucleus from non-VSG chromosome regions, suggesting that there is no dedicated VSG expression site. Strikingly, one chromosome contains approximately 40% of the VSG archive and is largely transcriptionally silent, potentially acting as the major reservoir of new VSG variants. Finally, we show that VSG expression can be detected from multiple small chromosomes. In summary, the new genome assembly provides a platform for understanding a potentially unusual operation of VSG expression and switching in T. congolense.

Trypanosoma congolense↗
PubMed1979

Non-specific induction of increased resistance in mice to Trypanosoma congolense and Trypanosoma brucei by immunostimulants.

Administration of the immunostimulants Corynebacterium parvum, Bacillus Calmette-Guérin (BCG) or Bordetella pertussis prior to, or at the same time as, challenge with Trypanosoma congolense significantly increased survival times in mice, both of trypano-susceptible (A/J) and trypano-resistant (C57Bl) strains. The increased survival time was associated with significant alterations in parasitaemia, which included lengthening of the pre-patent period, a delay in the time taken to reach the first peak of parasitaemia and a reduction in the level of parasitaemia. Similar results were obtained when these strains of mice were challenged with Trypanosoma brucei following pre-treatment with C. parvum. Thus, by the use of immunostimulants it was possible to reduce the susceptibility of mice to trypanosomiasis and the hope is that this can also be achieved with domestic livestock.

Animals↗
PubMed1979

Cyclical transmission of Trypanosoma brucei rhodesiense and Trypanosoma congolense by tsetse flies infected with culture-form procyclic trypanosomes.

Culture procyclic forms of Trypanosoma brucei rhodesiense and Trypanosoma congolense were fed to Glossina morsitans morsitans through artificial membranes. A very high percentage of the flies so fed produced established midgut infections, a proportion of which went on to develop into mature metacyclic trypanosomes capable of infecting mammalian hosts. The method offers a safe, clean way of infecting tsetse flies with African trypanosomes which reduces the need for trypanosome-infected animals in the laboratory.

Animals↗
PubMed1977

Inhibition of protein kinase activity from Trypanosoma cruzi and Trypanosoma gambiense by 3'-deoxyadenosine.

3'-Deoxydadenosine was found to be a potent inhibitor of nucleoside-stimulated protein kinase activity from culture forms of Trypanosoma cruzi and bloodstream forms of Trypanosoma gambiense. The type of inhibition by 3'-deoxyadenosine was competitive with respect to ATP. The inhibition constants for 3'-deoxyadenosine were determined to be 0.11mM and 0.085mM for the enzyme from T. cruzi and T. gambiense, respectively. The apparent Km value for ATP was 0.2mM for both enzymes. 2'-Deoxyadenosine was less effective as inhibitor of the protein kinase activity. The inhibition constants were calculated to be 0.8mM and 0.67mM, respectively.

Adenosine Triphosphate↗
PubMed1978

Effect of neocarzinostatin on the nucleus, kinetoplast and microtubules of Trypanosoma gambiense and Trypanosoma evansi.

The antibiotic neocarzinostatin (NCS) induces the anucleate form, not the dyskinetoplastic form, of Trypanosoma gambiense and Trypanosoma evansi. Light and electron microscopic studies indicated that production of the anucleate form is due to delay or inhibition of nuclear division. Excess pellicular microtubules are formed after treatment of trypanosomes with NCS, suggesting that in trypanosomes the microtubules replicate by induction, not by division. NCS also causes deformation of the axonemal and spindle microtubules. The K clone of T. evansi is more sensitive than the AK clone to the effects of NCS in inhibiting nuclear division and inducing the anucleate form.

Animals↗
PubMed1977

Cytofluorograf detection of Plasmodium yoelii, Trypanosoma gambiense, and Trypanosoma equiperdum by laser excited fluorescence of stained rodent blood.

Samples of rat blood infected with Plasmodium yoelii (3% parasitized erythrocytes), Trypanosoma gambiense, or Trypanosoma equiperdum (greater than 50 trypanosomes per microscope field at 400 X) were fixed with 0.5% glutaraldehyde in phosphate buffered saline, then stained with acridine orange (AO) at 10(-4), 10(-5), or 10(-6) M for 0 to 15 min at 5 C or 25 C and/or ethidium bromide (EB) at 0.05 mg/ml for 20 min at 25 C. Stained cells were analyzed with a laser Cytofluorograf (Bio/Physics Systems, Inc.) to determine if parasites could be detected and differentiated from blood cells by their fluorescent characteristics. Samples of uninfected rat blood with and without leukocytes and P. yoelii-infected blood without leukocytes were treated similarly. In addition, suspensions of T. gambiense and T. equiperdum without all blood cells were stained with AO or EB and analyzed with the Cytofluorograf, as were mixed suspensions of both trypanosome species. EB- but not AO-stained P. yoelii-infected erythrocytes had fluorescent characteristics different from most blood cells. Neither AO- nor EB-stained T. gambiense or T. equiperdum could be differentiated from host blood cells or from each other. The results are discussed with respect to the use of laser flow systems in the detection and analysis of bloodstream dwelling protozoan parasites.

Acridines↗
PubMed1975

Comparative studies of Trypanosoma vespertilionis Battaglia and Trypanosoma dionisii Bettencourt & França.

In diphasic blood agar media Trypanosoma vespertilionis developed spheroid clusters as compared to rather long, sausage-shaped (sometimes branched) clusters formed by Trypanosoma dionisii. The former species attained a greater population density (approximately 6 X 10(7) organisms/ml) than the latter (approximately 2 X 10(7) organisms/ml). Greater numbers of epimastigotes, some in active binary divisions, were observed during the logarithmic phase of growth, and morphologic changes occurred during cultivation which correlated with increased acidity and a depletion of glucose. Maximum numbers of trypomastigote forms were found during the stationary and early death phases. Most of the forms observed after 20 days were sphaeromastigotes. Glucose concentrations decreased to 0 M in T. vespertilionis and to 4.4 X 10(-5) M in T. dionisii cultures during the stationary and death phases. By the 12th day of incubation cultures of T. vespertilionis were more acid (pH 5.5) than those of T. dionisii vespertilionis and T. dionisii contained common and specific antigens. At least 2-3 common antigens were detected in extracts reacted against heterologous antisera. Specific antigens were observed as nonidentical lines formed by extracts reacted against homologous and heterologous antisera and with antisera absorbed with heterologous antigens. At least 2 specific antigens were evident in extracts of T. vespertilionis and 1 in extracts of T. dionisii.

Animals↗
PubMed2026

Natural killer (NK) cells with downregulated activating receptors and IL-10 production promote Trypanosoma cruzi T-cell responses in subjects in the Chronic phase of Trypanosoma cruzi infection: An exploratory immunological analysis.

BACKGROUND: Subjects with chronic Chagas disease and no signs of heart disease exhibit decreased NKp46 expression, high CD57 expression, and IL-10 production by NK cells. This study provides a detailed characterization of the phenotype and function of NK cells according to the severity of heart disease, and evaluates how these changes following treatment with benznidazole, as well as their association with Trypanosoma cruzi-specific T-cell responses. METHODS: The phenotype and function of NK cells in a cohort of 51 subjects infected with Trypanosoma cruzi and exhibiting varying degrees of heart disease were evaluated using high-dimensional flow cytometry and Boolean gating analysis. ELISPOT assays were performed to measure IFN-γ and IL-2 production in response to T. cruzi antigens, using CD56, CD4 and CD8-depleted PBMC. RESULTS: In contrast to individuals without heart disease, those with advanced cardiomyopathy have an increased number of NK cells that express the activating receptors NKp46 and CD16, as well as the differentiation marker CD57. NK cells in subjects with advanced cardiomyopathy were also found to be enriched in CD56+CD107+granzyme B+TNF-α+ cells and depleted of CD56+IL-10+ cells. The function of NK cells shifted towards monofunctionality in subjects with declining T. cruzi-specific antibodies following treatment with benznidazole. Eliminating CD56+ cells significantly decreased the number of IFN-γ-producing cells in response to T. cruzi. CONCLUSIONS: In chronic T. cruzi infection, NK-cell function may be balanced by the downregulation of activating receptors and IL-10 production, However, parasite persistence may desensitize the regulation of NK activating receptors, enabling NK cells to exert a potent polyfunctional cytotoxicity that potentially induce tissue damage.

Humans↗
PubMed1979

Use of micro-ELISA for quantitating antibody to Trypanosoma cruzi and Trypanosoma rangeli.

Of 229 residents of a Panamanian village where both Trypanosoma cruzi and Trypanosoma rangeli are endemic, 52% had antibody to one or both species by the enzyme-linked immunosorbent assay (ELISA), 26% were positive by complement fixation, 17% were positive by direct agglutination, and 32% were positive on the basis of clinical impression. Although the sensitivity of ELISA makes it the procedure of choice for sero-epidemiologic studies, there does appear to be some serologic cross-reactivity between the two species. Sera from 55 Panamanians and 33 Bolivians were reactive with antigens of T. cruzi and T. rangeli, thus making definitive diagnosis by serologic methods impossible. Although the presence of antibodies to both species suggests serologic cross-reactivity, the possibility of dual infection must be considered also. Fifty-four Panamanians and 20 Bolivians had antibody to only one species.

Antibodies↗
PubMed1979

Inhibition of bovine bone marrow granulocyte/macrophage colony formation in vitro by serum collected from cattle infected with Trypanosoma vivax or Trypanosoma congolense.

Serum collected from cattle infected with Trypanosoma vivax or Trypanosoma congolense inhibited bovine granulocyte/macrophage colony formation in methyl cellulose cultures. Maximum inhibition was caused by serum collected two and three weeks post infection. The degree of inhibition appeared to be related to the degree of parasitemia. Inhibition of erythroid colony formation by serum collected from these animals was not observed.

Animals↗
PubMed1978

The phosphoglucose isomerases of the bloodstream forms of Trypanosoma brucei and Trypanosoma vivax.

1. The phosphoglucose isomerases (PGI's) of the bloodstream forms of Trypanosoma brucei and T. vivax have been purified some 150-fold, using cellulose ion-exchange chromatography, gel filtration and isoelectric focussing. 2. The two trypanosome enzymes showed many similarities in kinetic properties, but differed from each other somewhat in thermal stability and in isoelectric point. 3. Both trypanosome enzymes differ from PGI's from other sources in having a higher Ki for the competitive inhibitor 6-phosphogluconate.

Animals↗
PubMed1977

Search for Trypanosoma rangeli in endemic areas of Trypanosoma cruzi in Argentina and Brazil.

Because the presence of Trypanosoma rangeli in Argentina and Brazil has not been confirmed, a serach was carried out in man and triatomine insects. Fifty-nine of 207 persons (28.5%) were infected when studied with one or more xenodiagnosis (40 Triatoma infestans/xenodiagnosis); 0.1% to 13% of 7,821 bugs' feces and 4% of 875 dissected midguts showed T. cruzi in Giemsa stained smears. One of 6,980 hemolymph samples and 1/875 salivary glands showed few flagellates which may have originated in the gut. They were not found in stained smears. Thirteen percent of 188 wild-caught domiciliary T. infestans showed only T. cruzi in the gut and feces. Although the presence of T. rangeli could not be demonstrated, the study indicates that examination of pooled hemolymph and random samples of salivary glands and midguts can be carried out together iwth the usual examination of extracted feces in any species of triatomine, including those with salivary glands lacking the pink color present in the genus Rhodnius. Unless this procedure is widely used it will not be possible to differentiate T. rangeli and other possible trypanosome infections from those of T. cruzi nor to determine, therefore, the true prevalence of Chagas' disease in a given human population.

Animals↗
PubMed1977

A comparative study of the responses of the thymus, spleen, lymph nodes and bone marrow of the albino rat to infection with Trypanosoma congolense and Trypanosoma brucei.

Using 90 albino rats, a comparison was made between the response to experimental infections of Trypanosoma brucei and T congolense of approximately three weeks duration by observation of parasitaemia, packed cell volume values, post mortem spleen and lymph weights, and histology of thymus, spleen, lymph nodes and bone marrow. In T congolense infection, phagocytosis of trypanosomes in the spleen appeared to be the main response of the host's haemopoietic tissues to the parasites, which were observed only intravascularly. In T brucei infection immunological responses occurred in the spleen and lymph nodes in addition to trypanosome phagocytosis. Trypanosomes were seen intercellularly in thymus, mediastinal tissue and lymph node sinuses and parasitaemia reached considerably higher values than in T congolense infection. Erythrophagocytosis in the spleen was the only histological feature which could account for the reduction in packed cell volume which occurred near death in both infections, medullary haemopoiesis being increased. Changes in the thymus, incorporating plasma cell production and depletion of cortical small lymphocytes, occurred in both infections.

Animals↗