Article
Microbiology
Christina Wilkinson, Meredith T. Morris
Summary: This study demonstrates a complex relationship between FBPase activity and extracellular glucose levels in Trypanosoma brucei, suggesting a potential additional role for FBPase in parasite metabolism. The differential expression of FBPase in various parasite cell lines and growth conditions implies regulation via post-translational modifications. These findings provide new insights into the metabolic pathways of Trypanosoma brucei.
Article
Biochemistry & Molecular Biology
Srinivasan Ramakrishnan, Rodrigo P. Baptista, Beejan Asady, Guozhong Huang, Roberto Docampo
Summary: In Trypanosoma brucei, down-regulation of Vps41 expression through RNAi leads to significant inhibition of endocytosis, affecting cell growth, while other functions of Vps41 in mammalian and yeast cells remain unaffected. The essentiality of TbVps41 suggests it as a potential drug target.
Article
Microbiology
Marina Schock, Steffen Schmidt, Klaus Ersfeld
Summary: Trypanosome brucei, the causative agent of African sleeping sickness, has a highly ordered subpellicular microtubule cytoskeleton associated with various proteins regulating morphology, motility, and virulence. Identified protein CAP50 colocalises with microtubules but not with the flagellum, playing a crucial role in maintaining cellular integrity. Depletion of CAP50, along with CAP52 and CAP42, results in defects in cytokinesis, morphology, and microtubule organization.
Article
Multidisciplinary Sciences
Amit Kumar Gaurav, Marjia Afrin, Xian Yang, Arpita Saha, S. K. Abdus Sayeed, Xuehua Pan, Zeyang Ji, Kam-Bo Wong, Mingjie Zhang, Yanxiang Zhao, Bibo Li
Summary: Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. TbRAP1, a telomere protein, has been shown to silence VSG genes by binding to dsDNA. However, the mechanism by which TbRAP1 allows the expression of a single active VSG gene was unknown. In this study, the researchers unexpectedly discovered an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. They found that TbRAP1 RRM, assisted by a specific patch, can recognize and bind to the 3'UTR sequences of VSG genes. Mutating the conserved residues in RRM abolished RNA binding activity, significantly decreased the level of active VSG RNA, and derepressed silent VSG genes. Their findings suggest a monoallelic expression mechanism for VSG genes, in which the abundant RNA of the active VSG gene antagonizes TbRAP1's silencing effect.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Cecilia Ortiz, Francesca Moraca, Marc Laverriere, Allan Jordan, Niall Hamilton, Marcelo A. Comini
Summary: G6PDH plays a crucial role in cell physiology by catalyzing the synthesis of NADPH(+) and ribose 5-phosphate. The study discovered that 16 alpha-brominated epiandrosterone is the most potent inhibitor of G6PDH in trypanosomatids. Further investigations showed that bromination at position 16 alpha of androstane derivatives yielded more potent T. cruzi G6PDH inhibitors.
Article
Infectious Diseases
Maria Lucia Sampaio Guther, Alan R. Prescott, Sabine Kuettel, Michele Tinti, Michael A. J. Ferguson
Summary: In Trypanosoma brucei, all nucleotide sugar biosynthesis is compartmentalized to the glycosomes in both lifecycle stages, unlike other eukaryotes. The study identifies the specific enzymatic biotransformations involved in this process and notes the heterogeneity of glycosome contents.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Microbiology
Oriana Villafraz, Helene Baudouin, Muriel Mazet, Hanna Kulyk, Jean-William Dupuy, Erika Pineda, Cyrille Botte, Daniel Ken Inaoka, Jean-Charles Portais, Frederic Bringaud
Summary: Trypanosomatids sequester glycolysis inside peroxisomes called glycosomes and have functional sugar nucleotide biosynthetic pathways in addition to cytosolic ones. The enzyme UDP-glucose pyrophosphorylase (UGP) is imported into glycosomes by piggybacking on phosphoenolpyruvate carboxykinase (PEPCK) without a known peroxisome-targeting signal, suggesting a unique mechanism for protein import. These findings shed light on the unconventional compartmentalization of metabolic pathways in trypanosomatids.
Article
Microbiology
Nuria W. Negrao, Logan P. Crowe, Brian S. Mantilla, Rodrigo P. Baptista, Sharon King-Keller, Guozhong Huang, Roberto Docampo
Summary: Trypanosoma brucei is the causative agent of African trypanosomiasis, and there is a need for new drugs due to limited treatment options and evidence of resistance. A phosphoinositide phospholipase C (TbPI-PLC-like) with an X and PDZ domain was discovered, similar to TbPI-PLC1. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity, but its knockdown affects the proliferation of trypanosomes.
Article
Immunology
Yan-Zi Wen, Hao-Tian Tang, Xiao-Li Cai, Na Wu, Jia-Zhen Xu, Bi-Xiu Su, Geoff Hide, Zhao-Rong Lun, De-Hua Lai
Summary: In this study, PAG3 was identified as a key nuclear gene involved in the slender to stumpy differentiation pathway of Trypanosoma brucei in the mammalian host. The loss of this gene might explain the inability of T. evansi and some T. equiperdum to differentiate and the adaptation to transmission cycles that bypass the tsetse vector or mechanical contact.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Chemistry, Medicinal
Miriam Yague-Capilla, Victor M. Castillo-Acosta, Cristina Bosch-Navarrete, Luis Miguel Ruiz-Perez, Dolores Gonzalez-Pacanowska
Summary: The study characterized the unique trypanosomal SAMHD1 orthologue TbHD52 as essential in maintaining pyrimidine dNTP homeostasis and contributing to cellular dTTP biosynthesis. Knockout of TbHD52 results in cellular dysfunction, which can be rescued by overexpression of human dCMP deaminase.
ACS INFECTIOUS DISEASES
(2021)
Article
Cell Biology
Miharisoa Rijatiana Ramanantsalama, Nicolas Landrein, Elina Casas, Benedicte Salin, Corinne Blancard, Melanie Bonhivers, Derrick R. Robinson, Denis Dacheux
Summary: A newly identified kinetoplastid-specific TF protein, TFK1, is found to play a key role in basal body maturation and cytokinesis in bloodstream form Trypanosoma brucei.
JOURNAL OF CELL SCIENCE
(2022)
Article
Immunology
Manon Geerts, Nick Van Reet, Sander Leyten, Raf Berghmans, Kat S. Rock, Theresa H. T. Coetzer, Lauren E-A Eyssen, Philippe Buscher
Summary: The newly developed T. b. gambiense inhibition ELISA (g-iELISA) based on the principle of antibody binding showed high specificity and sensitivity, making it suitable for regional laboratories in gHAT endemic countries for monitoring and surveillance.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Joseph T. Smith Jr, Brianna Tylec, Arunasalam Naguleswaran, Isabel Roditi, Laurie K. Read
Summary: This study reveals the importance of mitochondrial mRNA editing in the developmental regulation of Trypanosoma brucei. The researchers found that temperature reduction and depletion of the differentiation-repressive kinase RDK1 can affect the metabolism of Trypanosoma brucei by altering the editing of mitochondrial cytochrome mRNAs.
Article
Entomology
Zhiyuan Yang, Mai Shi, Xiaoli Zhang, Danyu Yao
Summary: This study dissected the genomic and transcriptomic profiles of T. brucei, identifying a panel of pathogenic proteins and microRNAs. The findings contribute to a better understanding of the parasite-host interaction mechanisms and provide new insights for designing preventive and therapeutic strategies for African trypanosomiasis.
Article
Microbiology
Brian S. Mantilla, Cristina Azevedo, Paul W. Denny, Adolfo Saiardi, Roberto Docampo
Summary: This study reveals the crucial role of histidine ammonia lyase (HAL) in the alkalinization of acidocalcisomes by binding to polyphosphate and regulating its function through lysine residues in the C-terminal region. HAL localization and inhibition by polyP demonstrate a mechanism for acidocalcisome alkalinization linked to amino acid metabolism.
Article
Chemistry, Medicinal
Diego Benitez, Estefania Dibello, Mariana Bonilla, Marcelo A. Comini
Summary: African trypanosomiasis is a major health problem in endemic countries and requires new drugs for treatment. In this study, a simple and economical high-throughput screening assay was developed using a bioluminescent cell line of the trypanosome parasite. The assay showed high sensitivity and accuracy in identifying compounds with potent anti-parasitic activity.
DRUG DEVELOPMENT RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Carolina L. Bellera, Manuel Llanos, Melisa E. Gantner, Santiago Rodriguez, Luciana Gavernet, Marcelo Comini, Alan Talevi
Summary: The COVID-19 pandemic has resulted in significant human and economic costs, making drug repurposing an attractive option for finding short-term treatments. Most current clinical trials are examples of drug repurposing, with caution needed to manage expectations and avoid overconfidence in conclusions drawn from scientific reports.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Multidisciplinary Sciences
Carlos A. Capoano, Luis Adrian Ortiz-Laquintana, Rosana Rodriguez-Casuriaga, Geraldine Schlapp, Maria Noel Meikle, Ana Paula Mulet, Martina Crispo, Ricardo Benavente, Adriana Geisinger
Summary: The Spats1 gene, although possibly a risk factor for male testicular health, is not individually essential for male fertility and spermatogenesis in mice. Phenotypic analysis of Spats1 knockout mice did not show overt differences compared to wild-type mice in terms of fertility, testicular content, and sperm quality.
Article
Multidisciplinary Sciences
A. P. Arevalo, R. Pagotto, J. L. Porfido, H. Daghero, M. Segovia, K. Yamasaki, B. Varela, M. Hill, J. M. Verdes, M. Duhalde Vega, M. Bollati-Fogolin, M. Crispo
Summary: The study demonstrated that ivermectin reduced the viral load and disease severity in mice infected with MHV, indicating its potential as a therapy for coronavirus diseases.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Analytical
Karen Perelmuter, Ines Tiscornia, Marcelo A. Comini, Mariela Bollati-Fogolin
Summary: The study validates the use of cytosolic rxYFP as a tool to monitor redox changes and optimize the production of recombinant proteins. The redox reporter cell lines showed a sensitive and reversible response to different redox stimuli. The results provide guidance for metabolic engineering or intervention strategies.
Article
Biochemistry & Molecular Biology
Ana Paula Arevalo, Romina Castelli, Manuel Ibarra, Martina Crispo, Victoria Calzada
Summary: This study evaluated the use of Sgc8-c aptamer as an imaging probe in a colon tumor xenograft mouse model, showing its excellent tumor imaging effect and high specificity. It has potential clinical applications for colon cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Agriculture, Dairy & Animal Science
Jose Renato S. Passos, Denise D. Guerreiro, Kamila S. Otavio, Pedro C. dos Santos-Neto, Marcela Souza-Neves, Federico Cuadro, Richard Nunez-Olivera, Martina Crispo, Maria Julia B. Bezerra, Renato F. Silva, Laritza F. Lima, Jose Ricardo Figueiredo, Ivan C. Bustamante-Filho, Alejo Menchaca, Arlindo A. Moura
Summary: The present study characterized the major proteome of preimplantation ovine embryos grown in vitro. The analysis identified proteins that are involved in translation, protein transport, and stabilization. Functional cluster analysis revealed differences between the in vitro and in vivo proteomes of sheep embryos, indicating that in vitro derived blastocysts have distinct protein profiles compared to those produced in vivo.
REPRODUCTION IN DOMESTIC ANIMALS
(2022)
Article
Genetics & Heredity
Matias Fabregat, Sofia Nino-Rivero, Sabrina Pose, Magdalena Cardenas-Rodriguez, Mariana Bresque, Karina Hernandez, Victoria Prieto-Echaguee, Geraldine Schlapp, Martina Crispo, Patricia Lagos, Natalia Lago, Carlos Escande, Florencia Irigoin, Jose L. Badano
Summary: This study reports the role of CCDC28B in regulating cilia length and behavioral phenotypes. By generating Ccdc28b mutant mice, the researchers found that these mice displayed a mild phenotype but exhibited clear social interaction defects and stereotypical behaviors. This provides a new opportunity to further investigate the genetic interactions in BBS and the association between ciliopathy and behavioral defects.
Article
Biochemistry & Molecular Biology
Jose Renato S. Passos, Denise D. Guerreiro, Kamila S. Otavio, Pedro C. dos Santos-Neto, Marcela Souza-Neves, Federico Cuadro, Richard Nunez-Olivera, Martina Crispo, Fabio R. Vasconcelos, Maria Julia B. Bezerra, Renato F. Silva, Laritza F. Lima, Jose Ricardo Figueiredo, Ivan C. Bustamante-Filho, Alejo Menchaca, Arlindo A. Moura
Summary: The present study evaluated the effects of in vitro maturation (IVM) on the proteome of cumulus-oocyte complexes (COCs) from ewes. The results showed that IVM caused upregulation and downregulation of proteins in COCs. Upregulated proteins in mature COCs after IVM were related to immune response, complement cascade, cell cycle, and extracellular matrix organization, while downregulated proteins in immature COCs after IVM were linked to metabolic processes, immune response, and complement cascade.
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2022)
Article
Virology
Ayelen Toro, Sofia Lage-Vickers, Juan Bizzotto, Felipe Vilicich, Agustina Sabater, Gaston Pascual, Sabrina Ledesma-Bazan, Pablo Sanchis, Maria Sol Ruiz, Ana Paula Arevalo, Jorge L. Porfido, Mercedes Abbate, Rocio Seniuk, Estefania Labanca, Nicolas Anselmino, Nora M. Navone, Daniel F. Alonso, Elba Vazquez, Martina Crispo, Javier Cotignola, Geraldine Gueron
Summary: This study demonstrates the important role of IFN-gamma and ISGs in the response to SARS-CoV-2 infection, suggesting their potential as adjuvant immunotherapy for COVID-19 patients. The analysis showed increased expression of IFN-gamma-associated pathways and ISGs in COVID-19-positive patients, which correlated with viral load and STAT1/JAK2 expression.
Article
Multidisciplinary Sciences
Hellen Daghero, Flora Doffe, Belen Varela, Victoria Yozzi, Jose Manuel Verdes, Martina Crispo, Mariela Bollati-Fogolin, Romina Pagotto
Summary: The NF-kappa B signaling pathway plays a crucial role in the intestine, protecting epithelial cells from harm while also mediating inflammatory diseases. Established NF-kappa B reporter organoids provide a valuable tool for evaluating anti-inflammatory compounds and exploring their effects in the small intestine.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Anabella A. Barrios, Camila Mouhape, Leonard Schreiber, Linyun Zhang, Juliane Nell, Mariana Suarez-Martins, Geraldine Schlapp, Maria Noel Meikle, Ana Paula Mulet, Tsui-Ling Hsu, Shie-Liang Hsieh, Gustavo Mourglia-Ettlin, Carlos Gonzalez, Martina Crispo, Thomas F. E. Barth, Cecilia Casaravilla, Stephen J. Jenkins, Alvaro Diaz
Summary: Cystic echinococcosis is a disease caused by larval stages of cestode parasites of the Echinococcus granulosus species cluster, with E. granulosus sensu stricto being the main infecting species. The parasites form bladder-like structures called hydatids in the internal organs of livestock ungulates and humans. The hydatids are protected by a large acellular laminated layer (LL) composed mainly of mucins. This study found that LL mucins injected into mice are taken up by liver macrophages called Kupffer cells, primarily through a receptor called Clec4F. These findings suggest that Kupffer cells play a role in clearing LL materials from the host.
INFECTION AND IMMUNITY
(2023)
Article
Microbiology
Paula Faral-Tello, Gonzalo Greif, Selva Romero, Andres Cabrera, Cristina Oviedo, Telma Gonzalez, Gabriela Libisch, Ana Paula Arevalo, Belen Varela, Jose Manuel Verdes, Martina Crispo, Yester Basmadjian, Carlos Robello
Summary: This study discovered Trypanosoma cruzi strains capable of vertical transmission, which have a higher transmission rate compared to strains of moderate or high virulence. The vertical transmission strains modulate placental gene expression, inducing anti-inflammatory responses and immune damage. This finding provides new insights into the mechanism of vertical transmission for this parasite.
MICROBIOLOGY SPECTRUM
(2023)
Article
Reproductive Biology
P. C. dos Santos-Neto, F. Cuadro, M. Souza-Neves, M. Crispo, A. Menchaca
Summary: In this study, the developmental competence, pregnancy outcomes, and embryo survival and birth rate of CRISPR/Cas microinjected zygotes in large scale programs in sheep were evaluated. The results showed that the developmental rate of microinjected zygotes was lower than non-injected zygotes, but similar outcomes were achieved when the embryos were transferred into the uterine horn instead of the oviduct. Furthermore, vitrification of CRISPR/Cas microinjected embryos did not significantly affect pregnancy rate, embryo survival rate, and birth rate.
Meeting Abstract
Biochemical Research Methods
Jorge Porfido, Maria Noel Meikle, Geraldine Schlapp, Alejo Menchaca, Martina Crispo
TRANSGENIC RESEARCH
(2022)