Review
Immunology
Kelli Monteiro da Costa, Leonardo Marques da Fonseca, Jhenifer Santos dos Reis, Marcos Andre Rodrigues da Costa Santos, Jose Osvaldo Previato, Lucia Mendonca-Previato, Leonardo Freire-de-Lima
Summary: Chagas' disease, caused by Trypanosoma cruzi, was described by Dr. Carlos Chagas in the early 20th century. One important discovery was trans-sialidase, an enzyme that masks the parasite's presence and dampens the immune response. Research into the disease has identified key events in the biochemical mechanism of T. cruzi-host cell interactions.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Gabriela de A. Burle-Caldas, Nailma S. A. dos Santos, Julia T. de Castro, Fernanda L. B. Mugge, Viviane Grazielle-Silva, Antonio Edson R. Oliveira, Milton C. A. Pereira, Joo Luis Reis-Cunha, Anderson Coqueiro dos Santos, Dawidson Assis Gomes, Daniella C. Bartholomeu, Nilmar S. Moretti, Sergio Schenkman, Ricardo T. Gazzinelli, Santuza M. R. Teixeira
Summary: Trans-sialidases (TS) are enzymes present on the surface of Trypanosoma cruzi, the causative agent of Chagas disease, and play a crucial role in the late stages of intracellular development and parasite egress. In this study, TS knockout parasites were generated using CRISPR-Cas9 technology, resulting in impaired parasite egress from infected cells. These TS mutants lost their ability to cause infection in vivo but provided full protection against a challenge infection with a virulent strain, indicating their potential as a live attenuated vaccine against Chagas disease.
Article
Microbiology
Gabriela de A. Burle-Caldas, Nailma S. A. dos Santos, Julia T. de Castro, Fernanda L. B. Mugge, Viviane Grazielle-Silva, Antonio Edson R. Oliveira, Milton C. A. Pereira, Joao Luis Reis-Cunha, Anderson Coqueiro dos Santos, Dawidson Assis Gomes, Daniella C. Bartholomeu, Nilmar S. Moretti, Sergio Schenkman, Ricardo T. Gazzinelli, Santuza M. R. Teixeira
Summary: Trans-sialidases play a crucial role in the virulence of Trypanosoma cruzi, and using CRISPR-Cas9, aTS mutant parasites were generated which lost infectivity in vivo but provided full protection against a challenge infection with a virulent strain.
Article
Chemistry, Medicinal
Ulises G. Castillo, Ayato Komatsu, Morena L. Martinez, Jenny Menjivar, Marvin J. Nunez, Yoshinori Uekusa, Yuji Narukawa, Fumiyuki Kiuchi, Junko Nakajima-Shimada
Summary: Chagas disease, caused by Trypanosoma cruzi, is considered one of the most infectious diseases in Central America. This study screened the anti-trypanosomal activity of plant species from Salvadoran flora, identifying four species with activity. A new flavanone compound, jaqueflavanone A, was isolated and found to exhibit anti-trypanosomal activity.
JOURNAL OF NATURAL MEDICINES
(2022)
Review
Immunology
Luciana L. Soprano, Maximiliano R. Ferrero, Thomas Jacobs, Alicia S. Couto, Vilma G. Duschak
Summary: Chagas disease caused by Trypanosoma cruzi is still a major problem in Latin America. Glycoproteins containing sulfated N-linked oligosaccharides play important roles in molecular recognition. Mice immunized with C-T showed pathological effects, indicating the importance of sulfated antigens in the disease. Antibodies specific for sulfotopes may serve as biomarkers for predicting the progression of cardiac Chagas disease.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Immunology
Juan Cruz Gamba, Carolina Roldan, Estefania Prochetto, Giuliana Lupi, Ivan Bontempi, Carolina Veronica Poncini, Monica Vermeulen, Ana Rosa Perez, Ivan Marcipar, Gabriel Cabrera
Summary: The study demonstrates the significant influence of MDSCs on the immune response during T. cruzi infection, even in vaccinated mice, impacting various immune cell populations. Targeting MDSCs may be an effective tool in vaccine design against T. cruzi and potentially other conditions characterized by immune system subversion.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fanny Mathias, Youssef Kabri, Damien Brun, Nicolas Primas, Carole Di Giorgio, Patrice Vanelle
Summary: Chagas disease caused by T. cruzi infection is a major public health problem in Latin America, resulting in 7000 annual deaths. This study synthesized ten new 1-substituted 2-nitropyrrole compounds and evaluated their biological activity. The derivatives showed good selectivity and activity against T. cruzi, but the maximum effect was lower than the reference drug.
Article
Plant Sciences
Nieves Martinez-Peinado, Javier E. Ortiz, Maria Jesus Pinazo, Joaquim Gascon, Alejandro Tapia, German Roitman, Jaume Bastida, Gabriela E. Feresin, Julio Alonso-Padilla
Summary: This study identified alkaloids with anti-T. cruzi activity from Habranthus brachyandrus collected in Argentina. The alkaloid ismine showed specific activity against the parasite and low toxicity against liver cells. These findings provide a new direction for the development of drugs for Chagas disease.
Article
Biochemistry & Molecular Biology
Naiara Dutra Barroso Gomes, Emanuel Paula Magalhaes, Lyanna Rodrigues Ribeiro, John Washington Cavalcante, Marcelo Morais Gomes Maia, Felipe Ramon Cunha da Silva, Arif Ali, Marcia Machado Marinho, Emmanuel Silva Marinho, Helcio Silva dos Santos, Alice Maria Costa Martins, Ramon Roseo Paula Pessoa Bezerra de Menezes
Summary: This study evaluated the activity of synthetic p-aminochalcones against T. cruzi and found that they have a trypanocidal effect by causing membrane damage and oxidative stress. Their mechanism of action may be related to inhibition of cruzain and TR.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Gevanio Bezerra de Oliveira Filho, Marcos Verissimo de Oliveira Cardoso, Aline Caroline da Silva Santos, Thiago Andre Ramos dos Santos, Ana Catarina Cristovao-Silva, Laura Gonzalez Rubio, Luiz da Silva Maia Neto, Paulo Gaio Leite, Fabiana Simao Machado, Luiz Carlos Alves, Fabio Andre Brayner, Valeria Rego Alves Pereira, Ana Cristina Lima Leite
Summary: Chagas disease is causing more deaths in the Americas than any other parasitic disease and is increasingly becoming a global health problem. A novel series of 4-thiazolidinones derivatives have shown increased anti-T. cruzi activity, indicating potential for treating the disease.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Chemistry, Multidisciplinary
Adriana Oliveira Souza, Johny Wysllas de Freitas Oliveira, Claudia Jessica Gonsalves Moreno, Mayra Jane Campos de Medeiros, Marilia Medeiros Fernandes-Negreiros, Flavia Roberta Monteiro Souza, Daniel Lima Pontes, Marcelo Sousa Silva, Hugo Alexandre Oliveira Rocha
Summary: This study analyzed silver nanoparticles containing fucoidan as an anti-Trypanosoma cruzi agent for the first time. The results showed that AgFuc nanoparticles have the ability to inhibit parasites and induce damage to their mitochondria. This suggests that AgFuc nanoparticles have potential therapeutic applications and further preclinical studies are needed.
Article
Pharmacology & Pharmacy
Ruben Martin-Escolano, Daniel Molina-Carreno, Javier Martin-Escolano, M. Paz Clares, Cristina Galiana-Rosello, Jorge Gonzalez-Garcia, Nuria Cirauqui, Jose M. Llinares, Maria Jose Rosales, Enrique Garcia-Espana, Clotilde Marin
Summary: Chagas disease, caused by Trypanosoma cruzi, is a potentially fatal infection that was previously limited to Latin America but has now become widespread globally. This study identified new effective agents against T. cruzi and evaluated their efficacy in vivo. Compound 15 was identified as a potential candidate for the development of new therapies for Chagas disease.
Article
Biochemistry & Molecular Biology
Alexa Prescilla-Ledezma, Fatima Linares, Mariano Ortega-Munoz, Lissette Retana Moreira, Ana Belen Jodar-Reyes, Fernando Hernandez-Mateo, Francisco Santoyo-Gonzalez, Antonio Osuna
Summary: This study utilizes AFM-based single molecule-force spectroscopy to detect and locate functional trans-sialidases on the surface of extracellular vesicles released by tissue-culture cell-derived trypomastigotes. By engineering AFM cantilevers with functionalized tips bearing anti-TS antibodies, molecular recognition of trans-sialidases using antibody-antigen interaction is achieved. The results demonstrate that the extracellular vesicles isolated from tissue-culture cell-derived trypomastigotes are enriched in trans-sialidases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Dimitris Matiadis, Tatiana Saporiti, Elena Aguilera, Xavier Robert, Christophe Guillon, Nallely Cabrera, Ruy Perez-Montfort, Marina Sagnou, Guzman Alvarez
Summary: In this study, a small library of functionalized compounds derived from curcuminoids were synthesized and evaluated for their trypanosomicidal activities. Compounds 4a and 4e showed significant activity against epimastigotes of Trypanosoma cruzi, while compound 6b effectively inhibited T. cruzi triosephosphate isomerase, demonstrating their potential as a new family of T. cruzi inhibitors with up to 16-fold higher potency compared to their curcuminoid precursors.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Plant Sciences
Javier E. Ortiz, Mauricio Pineiro, Nieves Martinez-Peinado, Patricia Barrera, Miguel Sosa, Jaume Bastida, Julio Alonso-Padilla, Gabriela E. Feresin
Summary: This study evaluated the anti-T. cruzi activity of the alkaloid candimine isolated from a plant, and assessed its combination effect with benznidazole, an existing drug. The results showed that candimine exhibited high anti-parasitic activity, and its combination with benznidazole enhanced its efficacy against T. cruzi, suggesting its potential as a new therapy for Chagas disease.
