Article
Immunology
Gabriela Venturini, Juliana M. Alvim, Kallyandra Padilha, Christopher N. Toepfer, Joshua M. Gorham, Lauren K. Wasson, Diogo Biagi, Sergio Schenkman, Valdemir M. Carvalho, Jessica S. Salgueiro, Karina H. M. Cardozo, Jose E. Krieger, Alexandre C. Pereira, Jonathan G. Seidman, Christine E. Seidman
Summary: This study reveals the molecular mechanisms and metabolic responses of Trypanosoma cruzi infection in cardiomyocytes. Infection activates the immune system and glycolysis pathway in cardiomyocytes, promoting intracellular infection and replication. These responses lead to heart dysfunction, cell death, and the development of cardiomyopathy.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Emanuella de Castro Andreassa, Marlon Dias Mariano dos Santos, Rafaela Wassmandorf, Helisa Helena Wippel, Paulo Costa Carvalho, Juliana de Saldanha da Gama Fischer, Tatiana de Arruda Campos Brasil de Souza
Summary: Understanding the biochemical changes associated with apoptosis in Trypanosoma cruzi is crucial for drug development and provides insights into the regulation of metabolic and cellular processes in nonmetazoan apoptotic cells. The study revealed that proteins associated with apoptosis in other species are also present in Trypanosoma cruzi, suggesting the preservation and application of apoptotic functions across different organisms, which could serve as potential targets for the treatment of Chagas disease.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2021)
Article
Parasitology
Eglys Gonzalez-Marcano, Hector Acosta, Wilfredo Quinones, Alfredo Mijares, Juan Luis Concepcion
Summary: Trypanosoma cruzi, the causative agent of Chagas' disease, undergoes multiple morphological and metabolic changes in its life cycle and can use both glucose and amino acids as energy sources. The glycolytic pathway in this parasite is compartmentalized in glycosomes and has a two-branched auxiliary system. The enzyme PPDK, which is the first enzyme in one branch of the pathway, exhibits hysteretic behavior, with its activity being affected by enzyme concentration, hydrogen ions, and substrate concentrations. Additionally, the enzyme's activity is influenced by the presence of its substrates and the cation ammonium, leading to the formation of a more active and complex form. These findings suggest that PPDK may function as a regulatory mechanism of the glycolytic pathway in response to different environments encountered by the parasite during its life cycle.
PARASITOLOGY RESEARCH
(2021)
Article
Multidisciplinary Sciences
Zongyuan Liu, Rebecca Ulrich vonBargen, April L. Kendricks, Kate Wheeler, Ana Carolina Leao, Krithivasan Sankaranarayanan, Danya A. Dean, Shelley S. Kane, Ekram Hossain, Jeroen Pollet, Maria Elena Bottazzi, Peter J. Hotez, Kathryn M. Jones, Laura-Isobel McCall
Summary: This study reveals the molecular mechanisms of Chagas disease treatment, including simultaneous effects on the pathogen and on host small molecule responses. It also highlights the link between persistent small molecule perturbation and clinical treatment failure in chronic infection.
NATURE COMMUNICATIONS
(2023)
Review
Chemistry, Analytical
Ketki Bagwe, Noah Gould, Kendall R. Johnson, Alexander R. Ivanov
Summary: Tissues and cell populations exhibit high levels of heterogeneity at the cellular level, making it important to analyze smaller sample sizes to capture subtle differences between cells. Capillary electrophoresis coupled with mass spectrometry (CE-MS) is a powerful technique for proteomics and metabolomics analysis at the single-cell level, and this review focuses on its applications and recent advances in sample preparation, separation, MS acquisition, and data analysis.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Laurent Gatto, Ruedi Aebersold, Juergen Cox, Vadim Demichev, Jason Derks, Edward Emmott, Alexander M. Franks, Alexander R. Ivanov, Ryan T. Kelly, Luke Khoury, Andrew Leduc, Michael J. MacCoss, Peter Nemes, David H. Perlman, Aleksandra A. Petelski, Christopher M. Rose, Erwin M. Schoof, Jennifer Van Eyk, Christophe Vanderaa, John R. R. Yates III, Nikolai Slavov
Summary: Analyzing proteins from single cells by tandem mass spectrometry (MS) has the potential to accurately quantify thousands of proteins across thousands of single cells. However, various factors affecting experimental design, sample preparation, data acquisition and analysis may undermine the accuracy and reproducibility of the results. Best practices, quality controls, and data-reporting recommendations are proposed to enhance the reliability of quantitative workflows for single-cell proteomics.
Article
Oncology
Giuliana Cavalloni, Caterina Peraldo-Neia, Annamaria Massa, Carlo Bergamini, Alessandro Trentini, Giovanni De Rosa, Lorenzo Daniele, Fabiola Ciccosanti, Carlo Cervellati, Francesco Leone, Massimo Aglietta
Summary: This study analyzed the proteomic profile of intrahepatic cholangiocarcinoma (ICC) derived from Italian patients and found differentially expressed proteins mainly involved in redox processes and cell structure and organization. The results suggest that impairment of the metabolic and antioxidant systems may play a key role in CCA development and progression.
Review
Biochemical Research Methods
Clemens Hermann, Leshern Karamchand, Jonathan M. Blackburn, Nelson C. Soares
Summary: The study provides an in-depth analysis of the cell envelope proteome in mycobacteria, contributing to the understanding of host-pathogen interactions and tuberculosis control efforts. It highlights the significance of the cell envelope proteome in infection and antibiotic resistance development, as well as the search for surface-exposed proteins that could be targeted by therapeutics and vaccines.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Food Science & Technology
Lena Mueller, Lucas Keuter, David Buecksteeg, Thomas Uebel, Markus Wilken, Lina Schuermann, Matthias Behrens, Hans-Ulrich Humpf, Melanie Esselen
Summary: The present study investigates the relationship between metabolic capacity and toxicity of the flavonoid nevadensin. The results show cell line dependent differences in toxic effect, with HepG2 and KG1 cells being more sensitive than HT29 cells. Glucuronidation was found to be a crucial metabolic pathway in vitro, and UGT1A6 and UGT1A1 were identified as responsible isoforms. This study highlights the importance of considering metabolic competence in the evaluation of toxic endpoints.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Biochemical Research Methods
Julien Slagboom, Rico J. E. Derks, Raya Sadighi, Govert W. Somsen, Chris Ulens, Nicholas R. Casewell, Jeroen Kool
Summary: In this study, the authors developed a new analytical strategy called high-throughput (HT) venomics, capable of performing a full proteomic analysis of snake venom in a short time. The strategy involves RP-HPLC-nanofractionation analytics, mass spectrometry analysis, in-solution tryptic digestion, and high-throughput proteomics. The authors also developed scripts to process and analyze the obtained data. They applied this strategy to venom samples from various medically important snake species and found it to be a valuable tool for studying venom variation.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemical Research Methods
Rafael Fogaca de Almeida, Aline Castro Rodrigues Lucena, Michel Batista, Fabricio Klerynton Marchini, Lyris Martins Franco de Godoy
Summary: Non-histone methylation plays a significant role in Trypanosoma cruzi, impacting important biological processes such as translation, RNA and DNA binding, and metabolism. The study provides insights into the potential impact of methylation on the biology of the parasite.
Article
Medicine, Research & Experimental
Helena Quintero-Pertuz, Ruben Veas-Albornoz, Ileana Carrillo, Fabiola Gonzalez-Herrera, Michel Lapier, Eduino Carbono-Delahoz, Esther del Olmo, Arturo San Feliciano, Ulrike Kemmerling, Claudio Olea-Azar, Carla Delporte, Juan D. Maya
Summary: Research on the Castanedia santamartensis plant in Colombia has identified several compounds with activity against Trypanosoma cruzi, a parasite that causes Chagas disease. Kaurenoic acid was found to be a major component in the plant's extracts, and it may act by disrupting the mitochondrial membrane potential in the parasite. This discovery opens up new avenues for potential treatments for Chagas disease.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Agriculture, Dairy & Animal Science
Logan G. Johnson, Chaoyu Zhai, Edward M. Steadham, Leah M. Reever, Kenneth J. Prusa, Mahesh N. Nair, Elisabeth Huff-Lonergan, Steven M. Lonergan
Summary: The tenderness of fresh pork is closely related to postmortem proteolysis. This study used liquid chromatography and mass spectrometry to evaluate the differences in myofibrillar sub-proteome between pork chops with different tenderness values. The results showed that different tenderness values were associated with distinct myofibrillar sub-proteomes.
JOURNAL OF ANIMAL SCIENCE
(2023)
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
Biochemistry & Molecular Biology
Aron Bartha, Zsuzsanna Darula, Gyoengyi Munkacsy, Eva Klement, Peter Nyirady, Balazs Gyorffy
Summary: This research used a proteotranscriptomic approach to differentiate normal and tumor tissues in clear cell renal cell carcinoma (ccRCC). Top genes over-expressed in ccRCC were identified using transcriptomic data of patients with malignant and normal tissue samples. Protein level analysis and mass spectrometry further validated the differential protein abundance of these genes. A minimal panel of proteins highly specific for ccRCC tissues was identified using transcriptomic and proteomic data.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Paulo Gaio, Melisa Gualdron-Lopez, Allysson Cramer, Lisia Esper, Jose Evaldo Rodrigues de Menezes Filho, Jader Santos Cruz, Mauro Martins Teixeira, Fabiana Simao Machado
Summary: This study found that SOCS2 plays a crucial role in regulating the immune response during Trypanosoma cruzi infection and maintaining the balance between inflammatory cells and immune tolerogenic cells.
CLINICAL IMMUNOLOGY
(2022)
Review
Microbiology
Paul A. M. Michels, Melisa Gualdron-Lopez
Summary: Glycosomes are organelles unique to Kinetoplastea and Diplonemea that contain enzymes of the glycolytic pathway and other metabolic pathways, with remarkable features in biogenesis and structure. Despite extensive research, many questions remain about the biological roles, heterogeneity, and properties of glycosomes and peroxisomes.
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mustafa M. Aldfer, Tahani A. AlSiari, Hamza A. A. Elati, Manal J. Natto, Ibrahim A. Alfayez, Gustavo D. Campagnaro, Bashiru Sani, Richard J. S. Burchmore, George Diallinas, Harry P. De Koning
Summary: The study of transporters, specifically nucleoside transporters, presents unique challenges and requires specific systems for analysis. This study describes the development of a system, using CRISPR/Cas9 technology, to delete and reintroduce nucleoside transporters in Leishmania mexicana, providing a null background for the expression and characterization of individual transporter genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Maura Rojas-Pirela, Diego Andrade-Alviarez, Lisvaneth Medina, Christian Castillo, Ana Liempi, Jesus Guerrero-Munoz, Yessica Ortega, Juan Diego Maya, Veronica Rojas, Wilfredo Quinones, Paul A. Michels, Ulrike Kemmerling
Summary: MicroRNAs (miRNAs) are a group of small non-coding RNA molecules that regulate gene expression. They play a crucial role in the pathogenesis of diseases, including those caused by parasitic protists. Additionally, miRNAs have the potential to be used as targets for drug design and as diagnostic and prognostic markers for parasitic diseases.
Article
Cell Biology
Diego Andrade-Alviarez, Alejandro D. Bonive-Boscan, Ana J. Caceres, Wilfredo Quinones, Melisa Gualdron-Lopez, Michael L. Ginger, Paul A. M. Michels
Summary: Glycosomes, specialized peroxisomes found in certain protists, play a crucial role in glycolysis and other metabolic processes. The evolution and function of glycosomes have been studied using genomic and proteomic data from different euglenozoans. The results suggest that glycosomes were compartmentalized in a common ancestor of kinetoplastids and diplonemids, and that the divergence of peroxins is evident in all euglenozoans. The ability of kinetoplastids and diplonemids to adapt to changing marine environments is attributed to the selective advantages provided by glycosomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Microbiology
Maura Rojas-Pirela, Diego Andrade-Alviarez, Wilfredo Quinones, Maria Veronica Rojas, Christian Castillo, Ana Liempi, Lisvaneth Medina, Jesus Guerrero-Munoz, Alejandro Fernandez-Moya, Yessica Andreina Ortega, Sebastian Araneda, Juan Diego Maya, Ulrike Kemmerling
Summary: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through interaction with target mRNA's 3' untranslated regions (3' UTR), impacting stability and translation. They play a role in biological processes such as signal transduction, cell death, metabolism, and development. Dysregulated miRNA expression is associated with infectious diseases, particularly those caused by helminths, where miRNAs modulate the parasite-host interaction. This comprehensive review analyzes the role of miRNAs in helminth infections, focusing on immune regulation and its implications for diagnosis, prognosis, and therapeutic strategies.
Editorial Material
Biochemistry & Molecular Biology
Paul A. M. Michels, Michael L. Ginger
Summary: A recent study found that a protein complex, which is responsible for mitochondrial cristae formation, also drives the formation of intracytoplasmic membranes in alphaproteobacteria, indicating a bacterial origin for the biogenesis of mitochondrial cristae.
Article
Parasitology
Maura Rojas-Pirela, Andrea Delgado, Yossmayer d. C. Rondon-Guerrero, Ana J. Caceres, Paul A. M. Michels, Juan Luis Concepcion, Wilfredo Quinones
Summary: PAS domains are a family of domains present in various prokaryotic and eukaryotic organisms. In Trypanosoma cruzi, the phosphoglycerate kinase (PGK) isoform TcPAS-PGK, which contains a PAS domain, was found to be localized in glycosomes and enriched mitochondrial fraction. The PAS domain plays an important regulatory role in the catalytic activity of PGK in T. cruzi.
EXPERIMENTAL PARASITOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marzuq A. Ungogo, Mustafa M. Aldfer, Manal J. Natto, Hainan Zhuang, Robyn Chisholm, Katy Walsh, MarieClaire McGee, Kayhan Ilbeigi, Jamal Ibrahim Asseri, Richard J. S. Burchmore, Guy Caljon, Serge Van Calenbergh, Harry P. De Koning
Summary: African Animal Trypanosomiasis (AAT) is a fatal livestock disease in Sub-Saharan Africa caused by Trypanosoma brucei brucei, T. vivax, and T. congolense. Limited treatment options and resistance threaten the control of this disease. In this study, the adenosine transporters of T. vivax (TvxNT3) and T. congolense (TcoAT1/NT10) were characterized and their functional expression was demonstrated. The findings suggest that nucleoside chemotherapy for AAT is viable based on the similarities in nucleoside sensitivity among different parasite species and the interactions with nucleoside transporters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Zandile Nare, Tessa Moses, Karl Burgess, Achim Schnaufer, Malcolm D. Walkinshaw, Paul A. M. Michels
Summary: In this study, potent inhibitors of the glycolytic enzyme PFK were developed and found to be effective in killing Trypanosoma brucei and related protists. These inhibitors did not affect human PFKs or human cells. Changes in the metabolome of cultured trypanosomes were analyzed after treatment with a selected PFK inhibitor. The results provide insights into the metabolic network and enzyme properties of trypanosomes.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Maura Rojas-Pirela, Ulrike Kemmerling, Wilfredo Quinones, Paul A. M. Michels, Veronica Rojas
Summary: Trypanosomiases are devastating tropical diseases caused by Trypanosoma brucei and Trypanosoma cruzi, with no effective treatment currently available. Antimicrobial peptides (AMPs) synthesized by both prokaryotes and eukaryotes have shown activity against various pathogens, including parasitic protists. This review analyzes the potential of AMPs as therapeutic alternatives for trypanosomiasis treatment, emphasizing their possible application as candidates for the development of future natural anti-trypanosome drugs.
Article
Biochemistry & Molecular Biology
Ivana Rubic, Stefan Weidt, Richard Burchmore, Alan Kovacevic, Josipa Kules, Peter David Eckersall, Marin Torti, Ines Jovic, Mislav Kovacic, Jelena Gotic, Renata Baric Rafaj, Predrag Novak, Marko Samardzija, Vladimir Mrljak
Summary: This study utilized mass spectrometry-based analysis to compare changes in plasma metabolites between dogs with idiopathic dilated cardiomyopathy (iDCM) and healthy dogs. The findings revealed altered concentrations of various metabolites involved in the development of iDCM. These results will contribute to the detection and monitoring of pathophysiological mechanisms in the development of iDCM in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Janaina F. Nascimento, Rodolpho O. O. Souza, Mayke B. Alencar, Sabrina Marsiccobetre, Ana M. Murillo, Flavia S. Damasceno, Richard B. M. M. Girard, Leticia Marchese, Luis A. Luevano-Martinez, Renan W. Achjian, Jurgen R. Haanstra, Paul A. M. Michels, Ariel M. Silber
Summary: ATP hydrolysis plays a crucial role in various cellular processes including synthesis, transport, and polymerization of monomers. In the bloodstream form of Trypanosoma brucei, a single parasite produces approximately 6.0 x 10(11) molecules of ATP per cell cycle, with total biomass production accounting for about 63% of the energy budget. Translation is identified as the most energy-consuming process. These findings provide new insights into the energetic requirements of BSF trypanosomes during their cell cycle.
