scholarly journals Glycosylation of Trypanosoma cruzi TcI antigen reveals recognition by chagasic sera

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Niamh Murphy ◽  
Barrie Rooney ◽  
Tapan Bhattacharyya ◽  
Omar Triana-Chavez ◽  
Anja Krueger ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Periodate Oxidation ◽  
Heat Denaturation ◽  
Parasitic Disease ◽  
Small Surface ◽  
Genetic Lineages ◽  
Gastrointestinal Pathology ◽  
Endemic Malaria ◽  
Clinical Presentations ◽  
Host Tissues

Abstract Chagas disease is considered the most important parasitic disease in Latin America. The protozoan agent, Trypanosoma cruzi, comprises six genetic lineages, TcI-TcVI. Genotyping to link lineage(s) to severity of cardiomyopathy and gastrointestinal pathology is impeded by the sequestration and replication of T. cruzi in host tissues. We describe serology specific for TcI, the predominant lineage north of the Amazon, based on expression of recombinant trypomastigote small surface antigen (gTSSA-I) in the eukaryote Leishmania tarentolae, to allow realistic glycosylation and structure of the antigen. Sera from TcI-endemic regions recognised gTSSA-I (74/146; 50.7%), with no cross reaction with common components of gTSSA-II/V/VI recombinant antigen. Antigenicity was abolished by chemical (periodate) oxidation of gTSSA-I glycosylation but retained after heat-denaturation of conformation. Conversely, non-specific recognition of gTSSA-I by non-endemic malaria sera was abolished by heat-denaturation. TcI-specific serology facilitates investigation between lineage and diverse clinical presentations. Glycosylation cannot be ignored in the search for immunogenic antigens.

scholarly journals A Trypanosoma cruzi Small Surface Molecule Provides the First Immunological Evidence that Chagas' Disease Is Due to a Single Parasite Lineage

2002 ◽  
Vol 195 (4) ◽  
pp. 401-413 ◽  
Author(s):  
Javier M. Di Noia ◽  
Carlos A. Buscaglia ◽  
Claudia R. De Marchi ◽  
Igor C. Almeida ◽  
Alberto C.C. Frasch
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cross Reactivity ◽  
Economic Problem ◽  
Future Research ◽  
Biological Traits ◽  
Small Surface ◽  
Genetic Lineages ◽  
Human Infections ◽  
Glycosylphosphatidyl Inositol

Chagas' disease is a major health and economic problem caused by the protozoan Trypanosoma cruzi. Multiple independently evolving clones define a complex parasite population that can be arranged into two broad genetic lineages termed T. cruzi I and II. These lineages have different evolutionary origin and display distinct ecological and biological traits. Here we describe a novel molecule termed TSSA for trypomastigote small surface antigen that provides the first immunological marker allowing discrimination between lineages. TSSA is a surface, glycosylphosphatidyl inositol (GPI)-anchored mucin-like protein, highly antigenic during the infection. TSSA sequences from different parasite isolates reveal a population dimorphism that perfectly matches with the two T. cruzi lineages. Interestingly, this dimorphism is restricted to the central region of the molecule, which comprises the immunodominant B cell epitopes. This sequence variability has a major impact on TSSA antigenicity, leading to no immunological cross-reactivity between both isoforms for antibodies present either in immunization or infection sera. Furthermore, the absolute seroprevalence for TSSA in confirmed Chagasic patients is restricted to T. cruzi II isoform, strongly suggesting that human infections are due to this particular subgroup. Even though association of T. cruzi II with Chagas' disease has been proposed based on molecular markers, this is the first immunological evidence supporting this hypothesis. The implications of these results for the future research on Chagas' disease could be envisaged.

scholarly journals Lineage-specific rapid diagnostic tests can resolve Trypanosoma cruzi TcII/V/VI ecological and epidemiological associations in the Argentine Chaco

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Niamh Murphy ◽  
Natalia P. Macchiaverna ◽  
M. Victoria Cardinal ◽  
Tapan Bhattacharyya ◽  
Pascal Mertens ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Shared Epitope ◽  
Epitope Peptide ◽  
Small Surface ◽  
Genetic Lineages ◽  
Gran Chaco ◽  
Clinical Associations ◽  
Secondary Antibodies ◽  
Reservoir Hosts ◽  
Lineage Distribution

Abstract Background Trypanosoma cruzi, the protozoan agent of Chagas disease, is comprised of at least 6 genetic lineages (TcI-TcVI). Their geographical distribution, clinical associations and reservoir hosts are not fully elucidated, as genotyping is hampered due to the difficulty in isolating representative populations of organisms. Lineage-specific serological techniques may address these issues. Methods Trypanosoma cruzi lineage-specific serological assays were performed on human, canine, feline and armadillo sera from the Gran Chaco in northern Argentina, a region of ongoing transmission. Synthetic peptides representing lineage-specific epitopes of the trypomastigote small surface antigen (TSSA) were used in ELISA, and the TcII/V/VI shared epitope peptide (TSSApep-II/V/VI) was used in the Chagas Sero K-SeT rapid diagnostic test (RDT). Results Chagas Sero K-SeT RDT, using Protein G to detect human and canine IgG, was at least as sensitive as TSSApep-II/V/VI ELISA using specific secondary antibodies. For sera from humans TSSApep-II/V/VI seroprevalence by Chagas Sero K-SeT was 273/393 (69.5%), for dogs 48/73 (65.8%) and for armadillos 1/7 (14.3%); by ELISA for cats 5/19 (26.3%). The seroprevalence for humans was similar to that for Bolivian patients, amongst whom we previously observed an association of TSSApep-II/V/VI seropositivity with severity of cardiomyopathy. In humans, prevalence of TSSApep-II/V/VI recognition was associated with locality, and with increasing and decreasing age within the Qom and Creole populations, respectively. For dogs TSSApep-II/V/VI recognition was associated with being born before community-wide insecticide spraying (P = 0.05) and with Qom household (P < 0.001). Conclusions We show here that Chagas Sero K-SeT RDT can replace ELISA for TSSApep-II/V/VI serology of humans and dogs; for humans there were statistically significant associations between a positive Chagas Sero K-SeT RDT and being resident in Area IV, and for dogs association with Qom household or with being born before the mass spraying campaign; we also show that with cats the TcII/V/VI epitope can be detected by ELISA. We assessed the lineage distribution in an unprecedented 83% of the human T. cruzi-seropositive population. These results form the basis for more detailed studies, enabling rapid in-the-field surveillance of the distribution and clustering of these lineages among humans and mammalian reservoirs of T. cruzi infection.

scholarly journals Identification of Leucinostatins from Ophiocordyceps sp. as Antiparasitic Agents Against Trypanosoma cruzi

2021 ◽  
Author(s):  
Jean A. Bernatchez ◽  
Yun-Seo Kil ◽  
Elany Barbosa da Silva ◽  
Diane Thomas ◽  
Laura-Isobel McCall ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasitic Infection ◽  
Antiparasitic Activity ◽  
Gastrointestinal Pathology ◽  
Phenotypic Screen ◽  
Benthic Environment ◽  
Intracellular Amastigote ◽  
Kinetoplastid Parasite

Safe and effective treatments for Chagas disease, a potentially fatal parasitic infection associated with cardiac and gastrointestinal pathology and caused by the kinetoplastid parasite Trypanosoma cruzi, have yet to be developed. Benznidazole and nifurtimox, which are currently the only available drugs against T. cruzi, are associated with severe adverse effects and questionable efficacy in the late stage of the disease. Natural products have proven to be a rich source of new chemotypes for other infectious agents. We utilized a microscopy-based high-throughput phenotypic screen to identify inhibitors of T. cruzi from a library of natural product samples obtained from fungi procured through a Citizen Science Soil Collection Program (https://whatsinyourbackyard.org/), and the Great Lakes (USA) benthic environment. We identified five leucinostatins (A, B, F, NPDG C and NPDG D) as potent inhibitors of the intracellular amastigote form of T. cruzi. Leucinostatin B also showed in vivo efficacy in a mouse model of Chagas disease. Given prior reports that leucinostatins A and B have antiparasitic activity against the related kinetoplastid T. brucei, our findings suggest a potential cross-trypanocidal compound class and provide a platform for further chemical derivatization of a potent chemical scaffold against T. cruzi.

scholarly journals The Trypomastigote Small Surface Antigen from Trypanosoma cruzi Improves Treatment Evaluation and Diagnosis in Pediatric Chagas Disease

2017 ◽  
Vol 55 (12) ◽  
pp. 3444-3453 ◽  
Author(s):  
Virginia Balouz ◽  
Luciano J. Melli ◽  
Romina Volcovich ◽  
Guillermo Moscatelli ◽  
Samanta Moroni ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Surface Antigen ◽  
Rapid Assessment ◽  
Drug Efficacy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serological Tests ◽  
Small Surface ◽  
Content Type

ABSTRACTChagas disease is caused by the protozoan parasiteTrypanosoma cruzi. Assessment of parasitological cure upon treatment with available drugs relies on achieving consistent negative results in conventional parasitological and serological tests, which may take years to assess. Here, we evaluated the use of a recombinantT. cruziantigen termed trypomastigote small surface antigen (TSSA) as an early serological marker of drug efficacy inT. cruzi-infected children. A cohort of 78 pediatric patients born toT. cruzi-infected mothers was included in this study. Only 39 of the children were infected withT. cruzi, and they were immediately treated with trypanocidal drugs. Serological responses against TSSA were evaluated in infected and noninfected populations during the follow-up period using an in-house enzyme-linked immunosorbent assay (ELISA) and compared to conventional serological methods. Anti-TSSA antibody titers decreased significantly faster than anti-whole parasite antibodies detected by conventional serology both inT. cruzi-infected patients undergoing effective treatment and in those not infected. The differential kinetics allowed a significant reduction in the required follow-up periods to evaluate therapeutic responses or to rule out maternal-fetal transmission. Finally, we present the case of a congenitally infected patient with an atypical course in whom TSSA provided an early marker forT. cruziinfection. In conclusion, we showed that TSSA was efficacious both for rapid assessment of treatment efficiency and for early negative diagnosis in infants at risk of congenitalT. cruziinfection. Based upon these findings we propose the inclusion of TSSA for refining the posttherapeutic cure criterion and other diagnostic needs in pediatric Chagas disease.

scholarly journals The Trypomastigote Small Surface Antigen (TSSA) regulates Trypanosoma cruzi infectivity and differentiation

2017 ◽  
Vol 11 (8) ◽  
pp. e0005856 ◽  
Author(s):  
María de los Milagros Cámara ◽  
Gaspar E. Cánepa ◽  
Andrés B. Lantos ◽  
Virginia Balouz ◽  
Hai Yu ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Surface Antigen ◽  
Small Surface

scholarly journals Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

2015 ◽  
Vol 22 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Virginia Balouz ◽  
María de los Milagros Cámara ◽  
Gaspar E. Cánepa ◽  
Santiago J. Carmona ◽  
Romina Volcovich ◽  
...  
Keyword(s):  
Amino Acid ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Surface Antigen ◽  
Humoral Response ◽  
Antigenic Structure ◽  
Antigenic Determinants ◽  
Small Surface ◽  
Content Type ◽  
Surface Receptors

ABSTRACTThe trypomastigote small surface antigen (TSSA) is a mucin-like molecule fromTrypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide- and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acid-long peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathioneS-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease.

Immuno-enzymatic evaluation of the recombinant TSSA-II protein ofTrypanosoma cruziin dogs and human sera: a tool for epidemiological studies

Parasitology ◽  
2011 ◽  
Vol 138 (8) ◽  
pp. 995-1002 ◽  
Author(s):  
R. O. CIMINO ◽  
M. MONJE RUMI ◽  
P. RAGONE ◽  
J. LAUTHIER ◽  
A. ALBERTI D'AMATO ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cutaneous Leishmaniasis ◽  
Area Under Curve ◽  
High Performance ◽  
False Negative ◽  
Epidemiological Studies ◽  
Kappa Index ◽  
Small Surface ◽  
Epidemiological Surveys ◽  
Human Sera

SUMMARYThe rTSSA-II (recombinant Trypomastigote Small Surface II) antigen was evaluated by ELISA to detect anti-Trypanosoma cruziantibodies in sera from naturally infected dogs and humans. For this evaluation ELISA-rTSSA-II was standardized and groups were classified according to the results obtained through xenodiagnosis, ELISA and PCR. Sensitivity (Se), Specificity (Sp), Kappa index (KI) and area under curve (AUC) were determined. The Se was determined by using 14 sera from dogs infected withT. cruziVI (TcVI) whereas Sp was determined by using 95 non-chagasic sera by xenodiagnosis, ELISA-Homogenate and PCR. The performance of ELISA-rTSSA-II in dog sera was high (AUC=0·93 and KI=0·91). The Se was 92·85% (1 false negative) and Sp was 100%. Two sera from dogs infected with TcI and 1 with TcIII were negative. For patients infected withT. cruzi, reactivity was 87·8% (36/41), there was only 1 indeterminate, and Sp was 100%. Fifty-four sera from non-chagasic and 68 sera from patients with cutaneous leishmaniasis did not react with rTSS-II. ELISA-rTSSA-II showed a high performance when studying sera from naturally infected dogs and it also presented 100% Sp. This assay could be an important tool to carry out sero-epidemiological surveys on the prevalence ofT. cruzicirculating lineages in the region.

Transmigration of Trypanosoma cruzi Trypomastigotes through 3D Spheroids Mimicking Host Tissues

2019 ◽  
pp. 165-177 ◽  
Author(s):  
Matías Exequiel Rodríguez ◽  
Mariana Rizzi ◽  
Lucas Caeiro ◽  
Yamil Masip ◽  
Daniel O. Sánchez ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Tissues ◽  
3D Spheroids

scholarly journals Phylogenetic diversity of two common Trypanosoma cruzi lineages in the Southwestern United States

2021 ◽  
Author(s):  
Carlos A Flores-Lopez ◽  
Elizabeth A Mitchell ◽  
Carolina E Reisenman ◽  
Sahotra Sarkar ◽  
Philip C Williamson ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Sequence Data ◽  
Sequence Divergence ◽  
Single Copy ◽  
High Genetic Diversity ◽  
Genetic Lineages ◽  
Control Programs ◽  
The Usa

Trypanosoma cruzi is the causative agent of Chagas disease, a devastating parasitic disease endemic to Central and South America, Mexico, and the USA. We characterized the genetic diversity of T. cruzi circulating in five triatomine species (Triatoma gerstaeckeri, T. lecticularia, T. indictiva, T. sanguisuga and T. recurva) collected in Texas and Southern Arizona using nucleotide sequences from four single-copy loci (COII-ND1, MSH2, DHFR-TS, TcCLB.506529.310). All T. cruzi variants fall in two main genetic lineages: 75% of the samples corresponded to T. cruzi Discrete Typing Unit (DTU) I (TcI), and 25% to a North American specific lineage previously labelled TcIV-USA. Phylogenetic and sequence divergence analyses of our new data plus all previously published sequence data from those 4 genes collected in the USA, show that TcIV-USA is significantly different from any other previously defined T. cruzi DTUs. The significant level of genetic divergence between TcIV-USA and other T. cruzi lineages should lead to an increased focus on understanding the epidemiological importance of this lineage, as well as its geographical range and pathogenicity in humans and domestic animals. Our findings further corroborate the fact that there is a high genetic diversity of the parasite in North America and emphasize the need for appropriate surveillance and vector control programs for Chagas disease in southern USA and Mexico.

Uptake and destruction of intracellular forms of Trypanosoma cruzi by murine macrophages: An ultrastructural study

1984 ◽  
Vol 42 ◽  
pp. 740-741
Author(s):  
H. S. Pankratz ◽  
F. Villalta ◽  
F. Kierszenbaum
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Host Defense ◽  
Causative Agent ◽  
Ultrastructural Study ◽  
Cell Interaction ◽  
Phagocytic Cell ◽  
Phagocytic Cells ◽  
Intracellular Amastigote ◽  
Host Tissues

Very little is known about the outcome of the interaction of phagocytic cells with the intracellular (amastigote) form of Trypanosoma cruzi, the causative agent of Chagas’ disease. Work with this form of the parasite has been hampered by the difficulties associated with the isolation of sufficient numbers of undamaged amastigotes from infected host tissues. Because amastigotes are the only forms of T. cruzi capable of multiplying in mammalian hosts, studies on phagocytic cell interaction with T. cruzi amastigotes are relevant to the mechanisms of host defense against and dissemination of the parasite. The recent development in our laboratory of conditions to produce T. cruzi amastigotes in axenic ML-15HA medium has rendered it possible to conduct research with this form of the organism.

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