Article
Multidisciplinary Sciences
Adina Heinberg, Inbar Amit-Avraham, Vera Mitesser, Karina Simantov, Manish Goyal, Yuval Nevo, Sofia Kandelis-Shalev, Emilie Thompson, Ron Dzikowski
Summary: This study reveals that the deadliest form of human malaria, caused by Plasmodium falciparum, is able to evade the human immune response by selectively expressing a single variant of a surface antigen. The researchers found that a long noncoding RNA (lncRNA) transcribed from an intron of an active gene is implicated in the choice of the single active variant. They also identified a protein called PfTPx-1, which interacts with the lncRNA and is involved in gene activation. Furthermore, they show that PfTPx-1 plays a role in providing a redox-controlled nuclear microenvironment ideal for active transcription.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Maartje R. Inklaar, Roos M. de Jong, Ezra T. Bekkering, Hikaru Nagaoka, Felix L. Fennemann, Karina Teelen, Marga van de Vegte-bolmer, Geert-Jan van Gemert, Rianne Stoter, C. Richter King, Nicholas I. Proellochs, Teun Bousema, Eizo Takashima, Takafumi Tsuboi, Matthijs M. Jore
Summary: This study identifies a new target for malaria transmission-blocking vaccines, Domain 7 of Pfs230, which can induce antibodies to block parasite development in mosquitoes. The study also discovers a new monoclonal antibody, mAb 18F25.2a, that significantly reduces mosquito infection with Plasmodium.
Article
Biochemistry & Molecular Biology
Devadathan Valiyamangalath Sethumadhavan, Marta Tiburcio, Abhishek Kanyal, C. A. Jabeena, Gayathri Govindaraju, Krishanpal Karmodiya, Arumugam Rajavelu
Summary: This study reveals the role of a chromodomain-containing protein in regulating the expression of rifins in Plasmodium falciparum, which in turn impacts the formation of RBC rosettes.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Damian Madan, Rafael Rivera, Corrie Ortega, Justin C. Touchon, Corinna Kimball, Geert-Jan Van Gemert, Wouter Graumans, Stephanie Matsuura, Sean S. Parghi, David Bell, Teun Bousema, Chris Drakeley, Katharine A. Collins, Thomas R. Burkot
Summary: This study demonstrates that measuring spermatozoa quantity in female Anopheles mosquitoes is an effective approach to assess mosquito age, which can improve vector control strategies for mosquito-borne diseases.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Cell Biology
Christabel N. Hikaambo, Natalia Shakela, John G. Woodland, Kathryn J. Wicht, Kelly Chibale
Summary: Zoonotic and related infections pose a significant health threat to Africa, the world's second-most populous continent. Despite the challenges faced by drug discovery scientists, recent progress in identifying potential medicines across diverse disease areas brings optimism and indicates African-led scientific initiatives are making progress.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Nanoscience & Nanotechnology
Xinyi Wang, Yiwei Xie, Ning Jiang, Jingyi Wang, Hongrui Liang, Dingyuan Liu, Na Yang, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen
Summary: This study developed a targeted drug delivery system for malaria treatment by preparing ferrite nanoparticles with ferromagnetic properties and loading them with artemisinin and heparin. The nanoparticles effectively targeted parasite-infected erythrocytes and interfered with the release of merozoites, enhancing the inhibitory efficacy of the antimalarial drug. Furthermore, the heparin-coated nanoparticles showed stronger blocking capability against malaria compared to free heparin due to multivalent interactions with surface receptors on merozoites.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Infectious Diseases
Daniel J. Weiss, Amelia Bertozzi-Villa, Susan F. Rumisha, Punam Amratia, Rohan Arambepola, Katherine E. Battle, Ewan Cameron, Elisabeth Chestnutt, Harry S. Gibson, Joseph Harris, Suzanne Keddie, Justin J. Millar, Jennifer Rozier, Tasmin L. Symons, Camilo Vargas-Ruiz, Simon I. Hay, David L. Smith, Pedro L. Alonso, Abdisalan M. Noor, Samir Bhatt, Peter W. Gething
Summary: This study evaluated the impact of disruptions to malaria control on malaria incidence and mortality in Africa. Findings show that reductions in access to effective antimalarial drug treatment and insecticide-treated net coverage could lead to increased malaria burden, potentially doubling malaria mortality in 2020.
LANCET INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Hanrui Zhang, Jiantao Guo, Hongyang Li, Yuanfang Guan
Summary: This study presents a model that predicts artemisinin treatment resistance based on transcriptomic information. It demonstrates the robustness of the model across in vivo and in vitro measurements and identifies transcription biomarkers for artemisinin resistance. The study has significant implications for malaria treatment research.
Article
Multidisciplinary Sciences
Jessica N. McCaffery, Douglas Nace, Camelia Herman, Balwan Singh, Eric Mukomena Sompwe, Papy Mandoko Nkoli, Dieudonne Mumba Ngoyi, Gauthier Mesia Kahunu, Eric S. Halsey, Eric Rogier
Summary: A study conducted in the Democratic Republic of the Congo found a low prevalence of pfhrp2 and pfhrp3 gene deletions in blood samples from patients with Plasmodium falciparum infection. Single deletions of pfhrp2 and pfhrp3 were sporadically observed in the study sites, while dual deletions were not found. The use of HRP2-based RDTs still appears to be appropriate for these locations in DRC.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Haoyu Lang, Hao Wang, Haoqing Wang, Zhaopeng Zhong, Xianbing Xie, Wenhao Zhang, Jun Guo, Liang Meng, Xiaosong Hu, Xue Zhang, Hao Zheng
Summary: This study reveals that the honeybee gut microbiota inhibits the proliferation of microsporidia and protects against Nosema ceranae infection by targeting its redox system. The findings highlight the importance of gut symbionts in protecting against parasitism and present a genetically engineered symbiont-mediated RNAi system for inhibiting microsporidia infections in honeybees.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Rebecca L. Clements, Alexander A. Morano, Francesca M. Navarro, James P. McGee, Esrah W. Du, Vincent A. Streva, Scott E. Lindner, Jeffrey D. Dvorin
Summary: This study identifies a basal complex protein, PfBLEB, as a key player in gametocytogenesis. Parasites lacking PfBLEB are unable to form mature gametocytes, highlighting the importance of PfBLEB. The study also provides a potential molecular target for the eradication of malaria transmission.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Parasitology
Alyssa E. Barry
Summary: Researchers have developed innovative methods for single-cell sequencing of P. vivax infections, providing new insights into the intrahost diversity and evolution of the parasite.
TRENDS IN PARASITOLOGY
(2021)
Article
Biochemistry & Molecular Biology
David Bacelar Costa Junior, Janay Stefany Carneiro Araujo, Larissa de Mattos Oliveira, Flavio Simas Moreira Neri, Paulo Otavio Lourenco Moreira, Alex Gutterres Taranto, Amanda Luisa Fonseca, Fernando de Pilla Varotti, Franco Henrique Andrade Leite
Summary: Malaria, caused by Plasmodium spp., remains a significant public health issue with drug resistance limiting chemotherapy. By exploring essential therapeutic targets of the parasite, a potential new antimalarial molecule with activity comparable to artemether was identified through virtual screening. This molecule, previously used in traditional Chinese medicine, may offer a repurposing opportunity to expedite drug development. Molecular dynamics studies confirmed the stability of molecular interactions, paving the way for further research on new derivatives for in vitro and in vivo evaluation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Environmental Sciences
Ellie Sherrard-Smith, Peter Winskill, Arran Hamlet, Corine Ngufor, Raphael N'Guessan, Moussa W. Guelbeogo, Antoine Sanou, Rebecca K. Nash, Alexander Hill, Emma L. Russell, Mark Woodbridge, Patrick Tungu, Mara D. Kont, Tom Mclean, Christen Fornadel, Jason H. Richardson, Martin J. Donnelly, Sarah G. Staedke, Samuel Gonahasa, Natascha Protopopoff, Mark Rowland, Thomas S. Churcher
Summary: The study aimed at comparing the public health impact and cost-effectiveness of different malaria prevention measures through the use of mathematical modeling and empirical data, highlighting the importance of selecting vector control interventions based on local conditions and budget.
LANCET PLANETARY HEALTH
(2022)
Article
Chemistry, Medicinal
Jessica Poole, Lauren E. Hartley-Tassell, Christopher J. Day, Danielle Stanisic, Penny L. Groves, Sumana Chakravarty, B. Kim Lee Sim, Stephen L. Hoffman, Joe Tiralongo, Nicolai Bovin, Denise L. Doolan, Michael P. Jennings
Summary: The transmission of Plasmodium spp. sporozoites to the mammalian host is crucial for the development of malaria, yet the exact route of transmission and the host glycan structures involved are not fully understood. By analyzing the glycan structures recognized and bound by sporozoites from P. falciparum and P. yoelii, this study identified key host glycan structures for human and rodent Plasmodium spp. sporozoites. Understanding how these sporozoites interact with specific glycan structures could offer insight into the infectious disease and aid in the development of effective therapeutics.
ACS INFECTIOUS DISEASES
(2021)
Review
Biochemistry & Molecular Biology
Leticia Prates Roma, Marcel Deponte, Jan Riemer, Bruce Morgan
ANTIOXIDANTS & REDOX SIGNALING
(2018)
Article
Biochemistry & Molecular Biology
Verena Staudacher, Madia Trujillo, Tim Diederichs, Tobias P. Dick, Rafael Radi, Bruce Morgan, Marcel Deponte
Article
Biochemistry & Molecular Biology
Kristina Feld, Fabian Geissel, Linda Liedgens, Robin Schumann, Sandra Specht, Marcel Deponte
Article
Biochemistry & Molecular Biology
Gaetano Calabrese, Esra Peker, Prince Saforo Amponsah, Michaela Nicole Hoehne, Trine Riemer, Marie Mai, Gerd Patrick Bienert, Marcel Deponte, Bruce Morgan, Jan Riemer
Article
Multidisciplinary Sciences
Linda Liedgens, Jannik Zimmermann, Lucas Waschenbach, Fabian Geissel, Hugo Laporte, Holger Gohlke, Bruce Morgan, Marcel Deponte
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Jannik Zimmermann, Julian Oestreicher, Steffen Hess, Johannes M. Herrmann, Marcel Deponte, Bruce Morgan
Article
Biochemistry & Molecular Biology
Gino L. Turra, Luzia Schneider, Linda Liedgens, Marcel Deponte
Summary: Leishmania parasites pose challenges for gene disruption and tagging, but the CRISPR-Cas9 system has shown promise for gene manipulation. The glmS system, on the other hand, has limitations in achieving efficient knock-downs for episomal genes and does not cause detectable phenotypes for chromosomal genes.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jannik Zimmermann, Julian Oestreicher, Fabian Geissel, Marcel Deponte, Bruce Morgan
Summary: A novel high-throughput assay has been developed for rapid and semi-quantitative evaluation of glutathione-dependent oxidoreductase activity. This method combines genetic fusion constructs between glutathione transporter and redox-sensitive fluorescent protein, enabling rapid characterization of enzyme activity and structure-function relationships. The assay allows direct screening of glutaredoxin activity and efficient detection of enzyme activity with physiological substrates.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Robin Schumann, Eileen Bischoff, Severina Klaus, Sophie Moehring, Julia Flock, Sandro Keller, Kim Remans, Markus Ganter, Marcel Deponte
Summary: Mutations in PfKelch13, specifically the absence of the thiol group of residue C473, are essential for altering the susceptibility to artemisinin in the human malaria parasite Plasmodium falciparum. Different forms of PfKelch13 with distinct electrophoretic mobilities were detected, indicating potential unidentified post-translational modifications. Additionally, impaired folding of PfKelch13, leading to decreased abundance, is the central parameter for mutant selection rather than redox properties.
Article
Microbiology
Gino L. Turra, Linda Liedgens, Frederik Sommer, Luzia Schneider, David Zimmer, Jordi Vilurbina Perez, Sasa Koncarevic, Michael Schroda, Timo Muehlhaus, Marcel Deponte
Summary: The study investigates the differences in protein import and oxidative folding in the mitochondrial intermembrane space among different eukaryotic lineages, focusing on the Erv homologue LtErv in parasitic kinetoplastids. By generating mutants and analyzing redox interactomes, the research sheds light on parasite-specific intracellular structure-function relationships and implies implications for mitochondrial protein import in nonopisthokonts.
MICROBIOLOGY SPECTRUM
(2021)
Article
Biochemistry & Molecular Biology
Robin Schumann, Lukas Lang, Marcel Deponte
Summary: This study focuses on the reduction reaction of PfAOP in malaria parasites with hydroperoxides and peroxynitrite, revealing chemical reaction rate constants and thermodynamic parameters through molecular docking and experimental measurements, and pointing out that conformational changes may be the rate-limiting step for the enzyme catalysis.
Article
Biochemistry & Molecular Biology
Marvin Haag, Jessica Kehrer, Cecilia P. Sanchez, Marcel Deponte, Michael Lanzer
Summary: In this study, the redox potential of P. falciparum-infected erythrocytes was measured using parasite-encoded roGFP2 variants. The results showed a sudden shift from a reducing to an oxidizing environment in the infected erythrocytes, which was independent of the presence of hemoglobin S.
Article
Chemistry, Physical
Lukas Lang, Ann-Cathrin Wolf, Mareike Riedel, Lea Thibol, Fabian Geissel, Kristina Feld, Jannik Zimmermann, Bruce Morgan, Georg Manolikakes, Marcel Deponte
Summary: 1-Cys Prx is an enzyme that uses only one cysteine residue for the reduction of hydroperoxides, and it requires an external thiol for the reduction of a reactive sulfenic acid. This study compared the reaction mechanisms and kinetics of Prx5 and Prx6 enzymes from Plasmodium falciparum to investigate the hyperoxidation susceptibility and potential substrate promiscuity of 1-Cys Prx.
Article
Biochemistry & Molecular Biology
Eileen Bischoff, Lukas Lang, Jannik Zimmermann, Maximilian Luczak, Anna Maria Kiefer, Gereon Niedner-Schatteburg, Georg Manolikakes, Bruce Morgan, Marcel Deponte
Summary: Dimedone and its derivatives are selective probes for nucleophilic detection of sulfenic acids, but they also react with cyclic sulfenamides. Glutathione outcompetes dimedone as a nucleophile by several orders of magnitude. Therefore, the selectivity of dimedone labeling of cysteinyl residues inside living cells is challenged.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Cletus A. Wezena, Romy Alisch, Alexandra Golzmann, Linda Liedgens, Verena Staudacher, Gabriele Pradel, Marcel Deponte