Article
Microbiology
Colm P. Roster, Danielle Lavigne, Jillian E. Milanes, Emily Knight, Heidi D. Anderson, Sabrina Pizarro, Elijah M. Harding, Meredith T. Morris, Victoria C. Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C. Rees, Brian Dominy, Daniel C. Whitehead, Md Nasir Uddin, Steven W. Millward, James C. Morris
Summary: Glucose metabolism is critical for the survival of Trypanosoma brucei, and inhibitors of human enolase have been found to be effective against the parasite.
Article
Chemistry, Multidisciplinary
Xinyi Wang, Di Zhang, Ning Jiang, Xiaofeng Wang, Naiwen Zhang, Kai Zhang, Xiaoyu Sang, Ying Feng, Ran Chen, Na Yang, Qijun Chen
Summary: This study investigated the endocytosis of two noble metal nanoclusters in Trypanosoma brucei, highlighting their potential for anti-parasitic treatment. The results showed that the nanoclusters could be efficiently up-taken by T. brucei via a clathrin-dependent endocytosis pathway. The study also revealed that the different nanoclusters interacted with specific organelles and proteins within the parasite, providing insight into the mechanism of action for potential drug development.
Article
Chemistry, Medicinal
David Cisneros, Eduardo J. Cueto-Diaz, Tania Medina-Gil, Rebecca Chevillard, Teresa Bernal-Fraile, Ramon Lopez-Sastre, Mustafa M. Aldfer, Marzuq A. Ungogo, Hamza A. A. Elati, Natsumi Arai, Momoka Otani, Shun Matsushiro, Chiaki Kojima, Godwin U. Ebiloma, Tomoo Shiba, Harry P. de Koning, Christophe Dardonville
Summary: Research showed that modifying the mitochondrion-targeting cations and scaffold of TAO inhibitors affected their in vitro activity, with the addition of polar substituents in the tail region generally having a detrimental impact on enzyme and cellular activity.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Cell Biology
Stefan Gaussmann, Mohanraj Gopalswamy, Maike Eberhardt, Maren Reuter, Peijian Zou, Wolfgang Schliebs, Ralf Erdmann, Michael Sattler
Summary: In this study, the membrane interactions of PEX5 and PEX14 NTDs were characterized in vitro using membrane mimicking bicelles and nanodiscs, revealing weak interaction of PEX14 NTD with bicelles and multiple interaction sites of PEX5 NTD involving amphipathic alpha-helical regions. Interestingly, the interaction between PEX5 and PEX14 NTDs was found to be largely unaffected by the presence of the membrane, suggesting that docking of PEX5 to PEX14 at the membrane does not reduce the overall binding affinity between the two proteins in the assembly of the peroxisome translocon.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Aline A. Zuma, Emile dos Santos Barrias, Wanderley de Souza
Summary: This review discusses the basic biology of the pathogenic protozoa Trypanosoma cruzi and Trypanosoma brucei, highlighting their developmental stages and unique structural characteristics, which can potentially serve as chemotherapeutic targets. Understanding these aspects contributes to drug development for chemotherapy.
CURRENT PHARMACEUTICAL DESIGN
(2021)
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
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)
Article
Microbiology
Anuj Tripathi, Ujjal K. Singha, Ayorinde Cooley, Taneisha Gillyard, Evan Krystofiak, Siddharth Pratap, Jamaine Davis, Minu Chaudhuri
Summary: TbTim50 is essential for mitochondrial function, regulation of kDNA replication, and the cell cycle in the bloodstream form of T. brucei. Depletion of TbTim50 results in inhibited cell growth, changes in morphology, increased AMPK phosphorylation, and upregulation of stumpy marker genes. TbTim50 is a crucial therapeutic target for African trypanosomiasis.
Article
Multidisciplinary Sciences
Justin Y. Toh, Agathe Nkouawa, Saul Rojas Sanchez, Huafang Shi, Nikolay G. Kolev, Christian Tschudi
Summary: By targeting 86 transcripts through RNAi, 22 genes that positively or negatively regulate the progression towards infectivity in Trypanosoma brucei have been identified, including the previously unknown nucleic acid binding proteins CSD1 and CSD2. The study suggests a considerable overlap between the genes that regulate stumpy bloodstream form Trypanosoma and those that govern the development of metacyclic form parasites.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Roberto Docampo, Anibal Eugenio Vercesi
Summary: This review discusses the mechanisms of mitochondrial oxidant generation and removal, and the involvement of Ca2+ in trypanosome cell death, highlighting the need for further studies on ROS generation, defense mechanisms, and mitochondrial permeability transition pore in trypanosomatids.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Multidisciplinary Sciences
Yanika Borg, Sam Alsford, Vasos Pavlika, Alexei Zaikin, Darren N. Nesbeth
Summary: Kinetoplastid protozoa, with unique properties, have been shown to hold bioengineering potential. This study successfully constructed an oscillatory gene network in Trypanosoma brucei for the first time, laying the foundation for future synthetic biology research.
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)
Review
Immunology
Nava Raj Poudyal, Kimberly S. Paul
Summary: This review discusses the availability and uptake mechanisms of fatty acids in Trypanosoma brucei. Fatty acids can be synthesized by the parasite or acquired from the host's surroundings. Fatty acids are crucial for the growth and survival of the parasite and are implicated in the survival of specific proteins. The relative contribution of parasite-derived and host-derived fatty acids to T. brucei biology and the molecular mechanisms of fatty acid uptake are still poorly understood.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
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.
Review
Cell Biology
Bibo Li
Summary: Telomeres and subtelomeres play crucial roles in maintaining chromosome stability and adapting to environmental changes, particularly in the case of the Trypanosoma brucei parasite. The similarities and differences in telomere factors between T. brucei, human, and yeast cells are important for understanding genome stability mechanisms.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Environmental Sciences
Zahid Hassan, Martin Braster, Wilfred F. M. Roling, Hans Westerhoff
Summary: Arsenate-reducing microorganisms can mobilize arsenic into groundwater. A cultivation-based metagenomic strategy was developed to infer actual activities and bridge the knowledge gap between cultivation-independent and cultivation-dependent analyses. This study clarifies the mechanism for arsenic mobilization and redistribution in rural drinking water wells and highlights the potential risks and the need for appropriate bioremediation strategies. Rating: 8/10.
GEOMICROBIOLOGY JOURNAL
(2023)
Article
Chemistry, Organic
Robert N. Goldberg, Robert T. Giessmann, Peter J. Halling, Carsten Kettner, Hans Westerhoff
Summary: The measurement of apparent equilibrium constants K ' for enzyme-catalyzed reactions involves critical details that cannot be neglected in order to avoid systematic errors. Interferences, impurities, and failure to achieve equilibrium are significant factors to consider. Careful reporting of results, including substance identification, reaction specification, reaction conditions, equilibrium constant definition, nomenclature, symbols, units, and uncertainties, is of great importance. This document provides a general discussion on various aspects of equilibrium measurements and STRENDA recommendations regarding the measurements and reporting of results.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2023)
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
Endocrinology & Metabolism
Yanhua Liu, Hans V. Westerhoff
Summary: Inborn error of metabolism phenylketonuria (PKU) is typically caused by inactivation of phenylalanine hydroxylase (PAH). The reduced PAH activity results in elevated phenylalanine levels and phenylpyruvate in urine. Flux balance analysis (FBA) predicts reduced growth rate in PKU, unless tyrosine is supplemented. However, the PKU phenotype is brain-specific and can be treated by phenylalanine reduction instead of tyrosine supplementation. This study presents an extended FBA model that explains the brain specificity of the disease, the role of phenylpyruvate as a biomarker, the effect of excess phenylalanine on brain pathology, and the superiority of phenylalanine deprivation as therapy.
JOURNAL OF INHERITED METABOLIC DISEASE
(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
Mathematics
Hans V. V. Westerhoff
Summary: Dynamic variables in non-equilibrium systems of life are determined by catalytic activities, which are related to genome expression. Modulating gene expression or enzyme function through medicinal drugs is becoming increasingly important. Despite the complexity of cellular systems biology, there are simple principles guiding the control of variables such as fluxes, concentrations, and half-times. By using time-unit invariance, a multitude of laws governing the control coefficients of multiple variables by all catalytic activities can be derived. The control of these variables is determined by time, resulting in simple integer sums when the variables are at maximum, minimum, or steady states.
Article
Biology
David D. van Niekerk, Erik Rust, Frank Bruggeman, Hans V. Westerhoff, Jacky L. Snoep
Summary: By analyzing models from the JWS Online and Biomodels databases, we investigated the use of the disequilibrium ratio as an estimator for the flux control of a reaction. While no functional relationship was found, the disequilibrium ratio can still be used as an estimator for the maximal flux control of a reaction step. We further expanded the analysis by incorporating the overall pathway disequilibrium ratio in the expression, leading to explicit expressions for flux control coefficients.
Article
Biology
Hans V. Westerhoff
Summary: This article resolves the paradoxes between microbial growth rate, enzyme activity, and flux control coefficients. The study found that under optimization conditions, enzyme control coefficients can equal zero, and flux balance analysis effectively maximizes growth yield, thereby resolving these contradictions.
Article
Physics, Multidisciplinary
Yanfei Zhang, Hans V. Westerhoff
Summary: Confronted with unfavorable output processes, free-energy transducers can shift to lower gears to reduce output per unit input. This option is well-known in machines but not appreciated in biology. This study extends thermodynamic principles to explain biological gear shifting and identifies mechanisms. It shows that gear shifting optimizes performance in living systems, allowing them to switch to catabolic pathways with lower ATP stoichiometry, thereby increasing ATP synthesis flux and ensuring continued growth even in challenging conditions.
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.
Article
Mathematical & Computational Biology
Yanhua Liu, Hans V. Westerhoff
Summary: This study develops a method called 'dynamic competition Flux Balance Analysis' (dcFBA), which can accommodate changes in cell density caused by competition. The experiment shows that signal transduction between cells is crucial for the co-existence of diverse cell types in multicellular organisms. Moreover, mutants that lose social characteristics can outgrow other cells, suggesting that 'asocialness' rather than enhanced growth rates may characterize cancer cells and organisms causing ecological blooms.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2023)
Article
Biology
Joost W. Aerts, Serban M. Sarbu, Traian Brad, Pascale Ehrenfreund, Hans V. Westerhoff
Summary: Movile Cave is a unique and challenging ecosystem where specialized prokaryotic communities can adapt to different subenvironments and respond to environmental changes in a relatively short time.
Article
Biology
Frank J. Bruggeman, Maaike Remeijer, Maarten Droste, Luis Salinas, Meike Wortel, Robert Planque, Herbert M. Sauro, Bas Teusink, Hans Westerhoff
Summary: This paper extends the scope of metabolic control analysis (MCA) to a whole-cell context, considering metabolism in the evolutionary context of growth-rate maximisation. The study shows that elementary flux modes (EFMs) naturally emerge as optimal metabolic networks in this context, and their control properties can be derived. The paper also demonstrates the estimation of flux control coefficients from proteomics and ribosome-profiling data. The findings provide insights into the control of metabolic enzymes on growth rate and contribute to the understanding of general principles in cell biochemistry.