Characterization of Novel <i>Trypanosoma cruzi</i>-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease
Chagas disease is caused by the parasite <i>Trypanosoma cruzi</i>. In humans, it evolves into a chronic disease, eventually resulting in cardiac, digestive, and/or neurological disorders. In the present study, we characterized a novel <i>T. cruzi</i> antigen named Tc323 (TcCL...
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MDPI AG
2024-01-01
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author | Micaela S. Ossowski Juan Pablo Gallardo Leticia L. Niborski Jessica Rodríguez-Durán Walter J. Lapadula Maximiliano Juri Ayub Raúl Chadi Yolanda Hernandez Marisa L. Fernandez Mariana Potenza Karina A. Gómez |
author_facet | Micaela S. Ossowski Juan Pablo Gallardo Leticia L. Niborski Jessica Rodríguez-Durán Walter J. Lapadula Maximiliano Juri Ayub Raúl Chadi Yolanda Hernandez Marisa L. Fernandez Mariana Potenza Karina A. Gómez |
author_sort | Micaela S. Ossowski |
collection | DOAJ |
description | Chagas disease is caused by the parasite <i>Trypanosoma cruzi</i>. In humans, it evolves into a chronic disease, eventually resulting in cardiac, digestive, and/or neurological disorders. In the present study, we characterized a novel <i>T. cruzi</i> antigen named Tc323 (TcCLB.504087.20), recognized by a single-chain monoclonal antibody (scFv 6B6) isolated from the B cells of patients with cardiomyopathy related to chronic Chagas disease. Tc323, a ~323 kDa protein, is an uncharacterized protein showing putative quinoprotein alcohol dehydrogenase-like domains. A computational molecular docking study revealed that the scFv 6B6 binds to an internal domain of Tc323. Immunofluorescence microscopy and Western Blot showed that Tc323 is expressed in the main developmental forms of <i>T. cruzi</i>, localized intracellularly and exhibiting a membrane-associated pattern. According to phylogenetic analysis, Tc323 is highly conserved throughout evolution in all the lineages of <i>T. cruzi</i> so far identified, but it is absent in <i>Leishmania</i> spp. and <i>Trypanosoma brucei</i>. Most interestingly, only plasma samples from patients infected with <i>T. cruzi</i> and those with mixed infection with <i>Leishmania</i> spp. reacted against Tc323. Collectively, our findings demonstrate that Tc323 is a promising candidate for the differential serodiagnosis of chronic Chagas disease in areas where <i>T. cruzi</i> and <i>Leishmania</i> spp. infections coexist. |
first_indexed | 2024-03-08T09:52:56Z |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-08T09:52:56Z |
publishDate | 2024-01-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-7ab70efc6c014c64a9b5f28606ab86552024-01-29T13:58:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01252120210.3390/ijms25021202Characterization of Novel <i>Trypanosoma cruzi</i>-Specific Antigen with Potential Use in the Diagnosis of Chagas DiseaseMicaela S. Ossowski0Juan Pablo Gallardo1Leticia L. Niborski2Jessica Rodríguez-Durán3Walter J. Lapadula4Maximiliano Juri Ayub5Raúl Chadi6Yolanda Hernandez7Marisa L. Fernandez8Mariana Potenza9Karina A. Gómez10Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Buenos Aires 1428, ArgentinaInstituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Buenos Aires 1428, ArgentinaInstituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Buenos Aires 1428, ArgentinaInstituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Buenos Aires 1428, ArgentinaInstituto Multidisciplinario de Investigaciones Biológicas de San Luis (IMIBIO-SL-CONICET), Facultad de Química Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis 5700, ArgentinaInstituto Multidisciplinario de Investigaciones Biológicas de San Luis (IMIBIO-SL-CONICET), Facultad de Química Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis 5700, ArgentinaHospital General de Agudos “Dr. Ignacio Pirovano”, Buenos Aires 1430, ArgentinaInstituto Nacional de Parasitología “Dr. Mario Fatala Chaben”, Buenos Aires 1063, ArgentinaInstituto Nacional de Parasitología “Dr. Mario Fatala Chaben”, Buenos Aires 1063, ArgentinaInstituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Buenos Aires 1428, ArgentinaInstituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres” (INGEBI-CONICET), Buenos Aires 1428, ArgentinaChagas disease is caused by the parasite <i>Trypanosoma cruzi</i>. In humans, it evolves into a chronic disease, eventually resulting in cardiac, digestive, and/or neurological disorders. In the present study, we characterized a novel <i>T. cruzi</i> antigen named Tc323 (TcCLB.504087.20), recognized by a single-chain monoclonal antibody (scFv 6B6) isolated from the B cells of patients with cardiomyopathy related to chronic Chagas disease. Tc323, a ~323 kDa protein, is an uncharacterized protein showing putative quinoprotein alcohol dehydrogenase-like domains. A computational molecular docking study revealed that the scFv 6B6 binds to an internal domain of Tc323. Immunofluorescence microscopy and Western Blot showed that Tc323 is expressed in the main developmental forms of <i>T. cruzi</i>, localized intracellularly and exhibiting a membrane-associated pattern. According to phylogenetic analysis, Tc323 is highly conserved throughout evolution in all the lineages of <i>T. cruzi</i> so far identified, but it is absent in <i>Leishmania</i> spp. and <i>Trypanosoma brucei</i>. Most interestingly, only plasma samples from patients infected with <i>T. cruzi</i> and those with mixed infection with <i>Leishmania</i> spp. reacted against Tc323. Collectively, our findings demonstrate that Tc323 is a promising candidate for the differential serodiagnosis of chronic Chagas disease in areas where <i>T. cruzi</i> and <i>Leishmania</i> spp. infections coexist.https://www.mdpi.com/1422-0067/25/2/1202Chagas disease<i>Trypanosoma cruzi</i><i>Leishmania</i> spp.diagnosisnovel antigenquinoproteins |
spellingShingle | Micaela S. Ossowski Juan Pablo Gallardo Leticia L. Niborski Jessica Rodríguez-Durán Walter J. Lapadula Maximiliano Juri Ayub Raúl Chadi Yolanda Hernandez Marisa L. Fernandez Mariana Potenza Karina A. Gómez Characterization of Novel <i>Trypanosoma cruzi</i>-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease International Journal of Molecular Sciences Chagas disease <i>Trypanosoma cruzi</i> <i>Leishmania</i> spp. diagnosis novel antigen quinoproteins |
title | Characterization of Novel <i>Trypanosoma cruzi</i>-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease |
title_full | Characterization of Novel <i>Trypanosoma cruzi</i>-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease |
title_fullStr | Characterization of Novel <i>Trypanosoma cruzi</i>-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease |
title_full_unstemmed | Characterization of Novel <i>Trypanosoma cruzi</i>-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease |
title_short | Characterization of Novel <i>Trypanosoma cruzi</i>-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease |
title_sort | characterization of novel i trypanosoma cruzi i specific antigen with potential use in the diagnosis of chagas disease |
topic | Chagas disease <i>Trypanosoma cruzi</i> <i>Leishmania</i> spp. diagnosis novel antigen quinoproteins |
url | https://www.mdpi.com/1422-0067/25/2/1202 |
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