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.
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, 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
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
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
Computer Science, Hardware & Architecture
Dinko Zidic, Toni Mastelic, Ivana Nizetic Kosovic, Mario Cagalj, Josip Lorincz
Summary: The usage of mobile communications has rapidly increased in the last decade, with mobility being one of its main aspects. However, rapid switching between different base station cells, known as ping-pong handover, causes negative effects such as increased signaling overhead and user dissatisfaction. This study analyzes the conditions under which ping-pong handovers occur and proposes a new empiric metric to evaluate the handover handling of pre-configured base stations.
Article
Parasitology
Maria F. Pacini, Camila Bulfoni Balbi, Brenda Dinatale, Florencia B. Gonzalez, Estefania Prochetto, Maria A. De Hernandez, Pamela Cribb, Cecilia Farre, Martin Espariz, Victor S. Blancato, Christian Magni, Ivan Marcipar, Ana R. Perez
Summary: A nasal vaccine based on a Trans-sialidase (TS) fragment plus the mucosal STING agonist c-di-AMP can stimulate the expression of cytokines in the nasopharyngeal-associated lymphoid tissue (NALT) and induce both mucosal and systemic immune responses to protect against Chagas disease.
Article
Chemistry, Medicinal
Lenci Karina Vazquez-Jimenez, Alma Delia Paz-Gonzalez, Alfredo Juarez-Saldivar, Maria Laura Uhrig, Rosalia Agusti, Alicia Reyes-Arellano, Benjamin Nogueda-Torres, Gildardo Rivera
Summary: This study conducted virtual screening using benzoic acid as a scaffold and identified 487 potential trans-sialidase inhibitors, with two lead compounds showing promising trans-sialidase inhibition values. Despite low trypanocidal activity, these compounds displayed high levels of trans-sialidase inhibition.
MEDICINAL CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
David Alexander Mitchell, Nadia Krieger
Summary: This study reparameterized the expressions for the relative rates of reaction of enantiomers in kinetic resolutions, making them easier to relate to the reaction mechanism.
BIOCHEMICAL ENGINEERING JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Nur Sulihatimarsyila Abd Wafti, Thomas Shean Yaw Choong, Harrison Lik Nang Lau, Robiah Yunus, Suraini Abd-Aziz, Nurliyana Abdul Raof
Summary: In this study, the reaction kinetics of palm-based polyol ester production catalyzed by commercial lipase N435 were analyzed. The results showed that N435 has a higher affinity towards TMP compared to HO-PME, and TMP has a lower inhibitory function. The obtained kinetics agreed well with the model of enzymatic transesterification with TMP and HO-PME as competitive inhibitors.
PROCESS BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Maria Florencia Pacini, Adrian Perdomini, Camila Bulfoni Balbi, Brenda Dinatale, Fernando E. Herrera, Ana Rosa Perez, Ivan Marcipar
Summary: The TS-GI proteins of the Trans-sialidase superfamily show promise as immunogens in vaccines against Trypanosoma cruzi. However, the antigenic variability of TS-GI among parasite lineages and its impact on vaccine development have not been previously analyzed. This study shows that TS-GI sequences have a high degree of identity and conserve the antigenic regions, suggesting their potential as vaccine targets. In silico analysis also reveals that different TS-GI-derived fragments have variable coverage and representation of epitopes, indicating the need for strategies to improve epitope coverage in TS-based vaccines.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Immunology
Julia T. Castro, Rory Brito, Natalia S. Hojo-Souza, Barbara Azevedo, Natalia Salazar, Camila P. Ferreira, Caroline Junqueira, Ana Paula Fernandes, Ronnie Vasconcellos, Jamille M. Cardoso, Rodrigo D. O. Aguiar-Soares, Paula M. A. Vieira, Claudia M. Carneiro, Bruno Valiate, Cristiane Toledo, Andres M. Salazar, Otavia Caballero, Joseli Lannes-Vieira, Santuza R. Teixeira, Alexandre B. Reis, Ricardo T. Gazzinelli
Summary: Immunization with TRASP protein associated with Poly-ICLC provides robust protection against Trypanosoma cruzi infection and induces high levels of T. cruzi-specific antibodies and IFN gamma-producing T cells. Protection is primarily mediated by CD8(+) T cells and IFN-gamma. The TRASP with Poly-ICLC vaccine showed similar efficacy to DNA/hAd5 vaccine in protecting dogs against T. cruzi challenge, but it is more advantageous due to pre-existing immunity to the adenovirus vector and cost-benefit for development and large-scale production.
Article
Microbiology
Suleiman Aminu, Gloria Dada Chechet, Samia S. Alkhalil, Mansour Sobeh, Rachid Daoud, Mthokozisi B. Simelane, Elewechi Onyike, Mohammed Auwal Ibrahim
Summary: In this study, the effects of beta-sitosterol on Trypanosoma congolense infection were investigated. The results showed that oral treatment with beta-sitosterol significantly reduced parasitemia and ameliorated parasite-induced anemia. It also reversed the increase in serum urea level and renal histopathological damage caused by the parasite. Beta-sitosterol down-regulated the expression of the TconTS1 gene. These findings suggest that beta-sitosterol could be a potential template for the design of novel trypanocides.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lissette Retana Moreira, Alexa Prescilla-Ledezma, Alberto Cornet-Gomez, Fatima Linares, Ana Belen Jodar-Reyes, Jorge Fernandez, Ana Karina Ibarrola Vannucci, Luis Miguel De Pablos, Antonio Osuna
Summary: This study characterized the proteomes and nanomechanical properties of extracellular vesicles released by different life stages of Trypanosoma cruzi, the etiologic agent of Chagas disease. The findings revealed significant differences in surface molecular cargos of vesicles between trypomastigotes and epimastigotes, with trypomastigotes exhibiting higher adhesion properties. This suggests a remarkable surface remodeling throughout the parasite's life cycle, potentially impacting the ability of extracellular vesicles to participate in cell communication in diverse infection niches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Maria Florencia Pacini, Florencia Belen Gonzalez, Brenda Dinatale, Camila Bulfoni Balbi, Silvina Raquel Villar, Cecilia Farre, Giuliana Lupi, Martin Espariz, Victor Sebastian Blancato, Christian Magni, Ivan Marcipar, Ana Rosa Perez
Summary: Intranasally-administered Trans-sialidase vaccines show promising immunogenicity and prophylactic efficacy against Trypanosoma cruzi, with TS + c-di-AMP formulation demonstrating the best protective capacity.
Article
Immunology
Yi Yang, Catherine R. Back, Melissa A. Graewert, Ayla A. Wahid, Harriet Denton, Rebecca Kildani, Joshua Paulin, Kristin Woerner, Wolgang Kaiser, Dmitri I. Svergun, Asel Sartbaeva, Andrew G. Watts, Kevin J. Marchbank, Jean M. H. van den Elsen
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Tristan Wagner, Gwenaelle Andre-Leroux, Valerie Hindie, Nathalie Barilone, Maria-Natalia Lisa, Sylviane Hoos, Bertrand Raynal, Brigitte Vulliez-Le Normand, Helen M. O'Hare, Marco Bellinzoni, Pedro M. Alzari
Review
Immunology
Marco Bellinzoni, Anne Marie Wehenkel, Rosario Duran, Pedro M. Alzari
MICROBES AND INFECTION
(2019)
Article
Multidisciplinary Sciences
Adria Sogues, Mariano Martinez, Quentin Gaday, Mathilde Ben Assaya, Martin Grana, Alexis Voegele, Michael VanNieuwenhze, Patrick England, Ahmed Haouz, Alexandre Chenal, Sylvain Trepout, Rosario Duran, Anne Marie Wehenkel, Pedro M. Alzari
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Michael J. Knight, Rachel E. Woolley, Anthony Kwok, Stuart Parsons, Hannah B. L. Jones, Christina E. Gulacsy, Polly Phaal, Omar Kassaar, Kieran Dawkins, Elizabeth Rodriguez, Andreia Marques, Leo Bowsher, Stephen A. Wells, Andrew Watts, Jean M. H. van den Elsen, Alison Turner, John O'Hara, Christopher R. Pudney
BIOCHEMICAL JOURNAL
(2020)
Article
Oncology
Lissete Sanchez-Magraner, James Miles, Claire L. Baker, Christopher J. Applebee, Dae-Jin Lee, Somaia Elsheikh, Shaimaa Lashin, Katriona Withers, Andrew G. Watts, Richard Parry, Christine Edmead, Jose Ignacio Lopez, Raj Mehta, Antoine Italiano, Stephen G. Ward, Peter J. Parker, Banafshe Larijani
Article
Biochemistry & Molecular Biology
Estefania Urdaniz, Mariano Martin, Florencia Payaslian, Lucas Alfredo Defelipe, Martin Dodes, Mariano Martinez, Pedro M. Alzari, Gabriela Cabrera, Marcelo Adrian Marti, Mariana Piuri
Summary: Bacteriophage endolysins play a crucial role in cell lysis and progeny release. The lysin A of mycobacteriophage can hydrolyze the bacterial cell wall and its activity is enhanced under acidic conditions. Mutant experiments showed that the central domain of the protein is essential for peptidoglycan hydrolysis.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2022)
Article
Biochemistry & Molecular Biology
Lenka Fule, Ruben Halifa, Celia Fontana, Odile Sismeiro, Rachel Legendre, Hugo Varet, Jean-Yves Coppee, Gerald L. Murray, Ben Adler, David R. Hendrixson, Alejandro Buschiazzo, Shuaiqi Guo, Jun Liu, Mathieu Picardeau
Summary: This study focused on the role of FlhF and FlhG in governing flagella regulation in the spirochete Leptospira. The research demonstrated that FlhG acts as a negative regulator of transcription of some flagellar genes in Leptospira and is not interchangeable between species. The findings suggest that FlhF and FlhG function differently in each bacterial species, including spirochetes.
MOLECULAR MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sonia Mondino, Fabiana San Martin, Alejandro Buschiazzo
Summary: Bacterial flagella are nanomachines that enable high-speed cell movement. Recent breakthroughs in 3D cryoEM methods have revealed novel structures and mechanistic insights into these flagella, challenging previous theories. These discoveries have advanced our understanding of the three major segments of the flagellum.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Microbiology
Matteo Tassinari, Thierry Doan, Marco Bellinzoni, Maialene Chabalier, Mathilde Ben-Assaya, Mariano Martinez, Quentin Gaday, Pedro M. Alzari, Eric Cascales, Remi Fronzes, Francesca Gubellini
Summary: This study provides important insights into the role and molecular organization of T7SSb, demonstrating the potential of B. subtilis as a model system for extensive structure-function studies of these secretion machineries.
Review
Biochemistry & Molecular Biology
Marcos Nieves, Alejandro Buschiazzo, Felipe Trajtenberg
Summary: All living organisms possess signaling devices for perceiving and adapting to the changing environment. Two-component systems play a role in regulating genetic and biochemical programs in response to specific signals. Recent advances in our molecular understanding of these systems have opened up possibilities for developing synthetic networks and biocomputing systems. This review focuses on the structural perspective of utilizing sensor and effector protein modules in two-component systems to construct new synthetic circuits.
BIOCHEMICAL JOURNAL
(2023)
Article
Multidisciplinary Sciences
Quentin Gaday, Daniela Megrian, Giacomo Carloni, Mariano Martinez, Bohdana Sokolova, Mathilde Ben Assaya, Pierre Legrand, Sebastien Brule, Ahmed Haouz, Anne Marie Wehenkel, Pedro M. Alzari
Summary: This study provides important insights into the mechanism of action of Cg1735 and Cg1604 in Corynebacteriales, demonstrating that Cg1604 activates PG hydrolysis by relieving the autoinhibition of Cg1735. These data contribute to understanding how as yet unidentified intracellular cell division signals regulate PG hydrolysis in this bacterial class.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Sofia Lima, Juan Blanco, Federico Olivieri, Juan A. Imelio, Marcos Nieves, Federico Carrion, Beatriz Alvarez, Alejandro Buschiazzo, Marcelo A. Marti, Felipe Trajtenberg
Summary: Phosphorylation carries chemical information in biological systems, and in two-component systems, uni- or bidirectional phosphoryl transfer reactions connect the sensor histidine kinase and response regulator. Directionality in phosphoryl transfer enables the construction of complex regulatory networks that optimize signal propagation and ensure the forward flow of information.
Article
Neurosciences
Gabriela I. Aparicio, Karina Formoso, Antonella Leon, Alberto C. Frasch, Camila Scorticati
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2020)
Article
Chemistry, Multidisciplinary
Marcos N. Morgada, Maria-Eugenia Llases, Estefania Giannini, Maria-Ana Castro, Pedro M. Alzari, Daniel H. Murgida, Maria-Natalia Lisa, Alejandro J. Vila
CHEMICAL COMMUNICATIONS
(2020)