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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/25/2/1202
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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.
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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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