Article
Multidisciplinary Sciences
Celine Christiansen, Deborah Maus, Ellen Hoppenz, Mateo Murillo-Leon, Tobias Hoffmann, Jana Scholz, Florian Melerowicz, Tobias Steinfeldt, Frank Seeber, Martin Blume
Summary: In this study, a human myotube-based in vitro culture model was developed to successfully culture functionally mature tissue cysts of Toxoplasma gondii, the parasites that cause chronic infections. The cultured cysts were orally infectious to mice and tolerant to various antibiotics and temperature stresses. Metabolomic analysis revealed significant changes in the metabolism of the cysts compared to the fast replicating tachyzoite forms, including increased levels of amino acids and decreased abundance of nucleobase- and tricarboxylic acid cycle-associated metabolites. This study provides a crucial tool for dissecting important host-parasite interactions and drug evasion mechanisms, as well as identifying new therapeutic strategies.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Jili Zhang, Jia Chen, Kun Lv, Bing Li, Biqing Yan, Lei Gai, Chaolu Shi, Xinnian Wang, Hongfei Si, Jiyu Zhang
Summary: Research suggests that myrislignan has anti-Toxoplasma gondii properties by affecting its oxidation-reduction process and inducing autophagy, ultimately leading to the parasite's death.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Injae Chung, Riccardo Serreli, Jason B. Cross, M. Emilia Di Francesco, Joseph R. Marszalek, Judy Hirst
Summary: Mitochondrial complex I plays a crucial role in oxidative phosphorylation and has been recognized as a potential drug target for ischemia-reperfusion injury, metabolic disorders, and cancers. A specific complex I inhibitor has been found to have a unique mechanism of inhibition, providing insights for future drug design.
Review
Parasitology
Rajshekhar Y. Gaji, Amanda K. Sharp, Anne M. Brown
Summary: Toxoplasma gondii is a life-threatening intracellular pathogen that depends on protein kinases for its life cycle. Research on Toxoplasma kinases aims to understand their functions and potentially develop therapeutics against this parasite.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Virology
Giulia Sibille, Anna Luganini, Stefano Sainas, Donatella Boschi, Marco Lucio Lolli, Giorgio Gribaudo
Summary: The pharmacological management of influenza virus infections is challenging due to the limited availability of effective drugs. This study characterized the anti-influenza activity of MEDS433, a small molecule inhibitor of hDHODH, a key cellular enzyme in the synthesis of pyrimidine. MEDS433 showed potent antiviral activity against different strains of influenza viruses and exhibited synergistic effects when combined with other anti-influenza drugs. These findings suggest that MEDS433 could be a potential candidate for host-targeting antivirals in the treatment of influenza virus infections.
Review
Oncology
Wanyan Wang, Jiayan Cui, Hui Ma, Weiqiang Lu, Jin Huang
Summary: Metabolic rewiring is a primary feature of cancer, with nucleotide biosynthesis being closely linked to cancer progression. Drugs targeting pyrimidine metabolism have limitations in efficacy and side effects, prompting the need for better strategies to inhibit pyrimidine metabolism in cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Jindriska Leischner Fialova, Katerina Honigova, Martina Raudenska, Lucie Miksatkova, Renata Zobalova, Jiri Navratil, Jana Smigova, Taraka Ramji Moturu, Tomas Vicar, Jan Balvan, Katerina Vesela, Nikita Abramenko, Zdenek Kejik, Robert Kaplanek, Jaromir Gumulec, Daniel Rosel, Pavel Martasek, Jan Brabek, Milan Jakubek, Jiri Neuzil, Michal Masarik
Summary: Mitochondria play a crucial role in cellular growth and function, and recent studies have challenged the notion that they are not involved in cancer growth. This study shows that pentamethinium salts, originally designed as mitochondrial probes, have a strong inhibitory effect on cancer cell proliferation and migration by interfering with mitochondrial respiration and causing oxidative stress. These findings suggest that pentamethinium salts could be potential novel anti-cancer agents.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Agriculture, Multidisciplinary
Thomas P. P. Selby, Andrew D. D. Satterfield, Atul Puri, Thomas M. M. Stevenson, D. Andrew Travis, Matthew J. J. Campbell, Andrew E. E. Taggi, Kenneth A. A. Hughes, James Bereznak
Summary: This paper describes the discovery and optimization process of a new herbicide with excellent weed control and safety on rice. It also introduces the proposed common name and the classification of this herbicide.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Matthew L. Blank, Jing Xia, Mary M. Morcos, Mai Sun, Pamela S. Cantrell, Yang Liu, Xuemei Zeng, Cameron J. Powell, Nathan Yates, Martin J. Boulanger, Jon P. Boyle
Summary: Research identified interactions between a single parasite effector and multiple target host proteins at the interface between the Toxoplasma gondii vacuole and the host mitochondria, some of which are critical for the HMA phenotype itself.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Parasitology
Yihan Wu, Zhu Ying, Jing Liu, Zhepeng Sun, Shuang Li, Qun Liu
Summary: This study identified and characterized the ANT protein in T. gondii. Depletion of TgANT inhibited parasite growth, impaired mitochondrial and apicoplast biogenesis, and resulted in abnormal cell division.
PARASITES & VECTORS
(2022)
Article
Chemistry, Medicinal
P. Holland Alday, Erin McConnell, Jan M. Boitz Zarella, Rozalia A. Dodean, Papireddy Kancharla, Jane X. Kelly, J. Stone Doggett
Summary: Acridone derivatives exhibit potent activity against T. gondii, inhibiting its proliferation at effective concentrations and showing efficacy in a murine model of systemic toxoplasmosis. They represent a promising new class of preclinical compounds for the treatment of toxoplasmosis.
ACS INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Rajib Acharjee, Keith K. Talaam, Endah D. Hartuti, Yuichi Matsuo, Takaya Sakura, Bundutidi M. Gloria, Shinya Hidano, Yasutoshi Kido, Mihoko Mori, Kazuro Shiomi, Masakazu Sekijima, Tomoyoshi Nozaki, Kousuke Umeda, Yoshifumi Nishikawa, Shinjiro Hamano, Kiyoshi Kita, Daniel K. Inaoka
Summary: Toxoplasma gondii is a protozoan parasite that infects a large portion of the global human population. A new potential drug target, TgMQO, has been identified in this study, and a novel expression system was developed to study its characteristics. Ferulenol, an MQO inhibitor, showed promising inhibitory effects on TgMQO, with distinct binding sites from other known inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Aarin M. Huffman, Joseph A. Ayariga, Audrey Napier, Boakai K. Robertson, Daniel A. Abugri
Summary: This study reports the anti-Toxoplasma and anti-invasion properties of Dihydroquinine (DHQ). DHQ has high selective parasiticidal effects against the growth of T. gondii tachyzoites. DHQ has the potential to be an effective and safe lead for the treatment of toxoplasmosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Melissa A. Sleda, Zhu-Hong Li, Ranjan Behera, Baihetiya Baierna, Catherine Li, Jomkwan Jumpathong, Satish R. Malwal, Makoto Kawamukai, Eric Oldfield, Silvia N. J. Moreno
Summary: This study investigates the synthesis of polyprenyl diphosphate in Toxoplasma gondii and identifies the enzyme TgCoq1 as a key player in this process. The growth of TgCoq1 mutants is impaired, but can be rescued by complementation with a homologous gene or a related enzyme. Additionally, a bisphosphonate is found to inhibit T. gondii growth, which can be reversed by supplementation with long-chain ubiquinone. Importantly, the bisphosphonate also protects mice against lethal T. gondii infection.
Article
Biochemistry & Molecular Biology
Zisis Koutsogiannis, John G. Mina, Christin A. Albus, Matthijs A. Kol, Joost C. M. Holthuis, Ehmke Pohl, Paul W. Denny
Summary: The study found that the ceramide synthases TgCerS1 and TgCerS2 in Toxoplasma gondii function differently, with TgCerS1 being catalytically active and TgCerS2 being inactive. While TgCerS1 is important but not indispensable for parasite growth, TgCerS2 plays a greater role in parasite fitness. This unique arrangement of ceramide synthase isoforms in Toxoplasma and other Apicomplexa highlights their unusual biology.
Article
Microbiology
Miryam A. Hortua Triana, Karla M. Marquez-Nogueras, Le Chang, Andrew J. Stasic, Catherine Li, Kevin A. Spiegel, Amrita Sharma, Zhu-Hong Li, Silvia N. J. Moreno
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2018)
Article
Microbiology
Le Chang, Eric J. Dykes, Jianhua Li, Silvia N. J. Moreno, Miryam Andrea Hortua Triana
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2019)
Article
Microbiology
Manuel F. Garavito, Heidy Y. Narvaez-Ortiz, Dania Camila Pulido, Monika Loeffler, Howard S. Judelson, Silvia Restrepo, Barbara H. Zimmermann
FRONTIERS IN MICROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Paula Galeano Garcia, Barbara H. Zimmermann, Chiara Carazzone
Article
Cell Biology
Stephen A. Vella, Christina A. Moore, Zhu-Hong Li, Miryam A. Hortua Triana, Evgeniy Potapenko, Silvia N. J. Moreno
Summary: Toxoplasma gondii relies on calcium signaling for motility and egress from host cells, utilizing both intracellular and extracellular calcium sources.
Article
Microbiology
Geetha Kannan, Pariyamon Thaprawat, Tracey L. Schultz, Vern B. Carruthers
Summary: This study demonstrates that Toxoplasma gondii bradyzoites can ingest host-derived cytosolic proteins across the cyst wall, providing insight into how the parasite obtains resources within infected cells. Disruption of a parasite protease enhances accumulation of host-derived protein within the chronic-stage parasites, suggesting a potential role in supporting the parasite's persistence.
Review
Biology
Olivia L. McGovern, Yolanda Rivera-Cuevas, Vern B. Carruthers
Summary: Research on endocytosis in protozoan parasites, including malaria parasites and Toxoplasma gondii, is still in early stages. Malaria parasites acquire nutrients by internalizing hemoglobin from infected red blood cells, while the active endocytic system of Toxoplasma gondii was recently discovered. Future studies will help uncover the molecular basis and biological significance of endocytosis in Toxoplasma gondii.
Article
Biology
Karla Marie Marquez-Nogueras, Miryam Andrea Hortua Triana, Nathan M. Chasen, Ivana Y. Kuo, Silvia N. J. Moreno
Summary: This study identified a novel ion channel, TgTRPPL-2, in Toxoplasma gondii that plays a role in Ca2+ signaling and may stimulate parasite motility, invasion, and egress through a Ca2+ signaling cascade. TgTRPPL-2 represents a potential target for combating toxoplasmosis.
Article
Microbiology
My-Hang Huynh, Vern B. Carruthers
Summary: The lytic cycle of Toxoplasma gondii involves repetitive processes of cell invasion, replication, egress, and re-invasion. This study focuses on the molecular mechanisms underlying egress, particularly the role of PLP1 and FNTs in triggering a decrease in parasitophorous vacuole (PV) pH, which is necessary for successful egress.
Article
Microbiology
Joshua Mayoral, Rebekah B. Guevara, Yolanda Rivera-Cuevas, Vincent Tu, Tadakimi Tomita, Julia D. Romano, Leslie Gunther-Cummins, Simone Sidoli, Isabelle Coppens, Vernon B. Carruthers, Louis M. Weiss
Summary: This study investigates the interaction between the secreted protein GRA64 of Toxoplasma gondii and host endosomal sorting complexes required for transport (ESCRT), and reveals the important role of GRA64 in tissue cyst formation. This study lays the foundation for further understanding the mechanics and consequences of host ESCRT-parasite protein interactions.
Review
Microbiology
Andrew J. Stasic, Silvia N. J. Moreno, Vern B. Carruthers, Zhicheng Dou
Summary: The PLVAC of T. gondii, which represents its lysosomal compartment, plays important roles in ion storage and homeostasis, endocytosis, exocytosis, and autophagy.
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2022)
Article
Cell Biology
Julia D. Romano, Joshua Mayoral, Rebekah B. Guevara, Yolanda Rivera-Cuevas, Vern B. Carruthers, Louis M. Weiss, Isabelle Coppens
Summary: Intracellular pathogens, such as Toxoplasma gondii, manipulate host cells to exploit cellular resources. The parasite sequesters host nutrient-filled organelles into its parasitophorous vacuole (PV) through deep invaginations of the PV membrane (PVM). The parasite utilizes the host ESCRT-III and Vps4A to create PVM buds and vesicles.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Dana Aghabi, Megan Sloan, Grace Gill, Elena Hartmann, Olga Antipova, Zhicheng Dou, Alfredo J. Guerra, Vern B. Carruthers, Clare R. Harding
Summary: Iron serves as a cofactor in enzymes, but incorrect storage leads to dangerous oxygen radicals. The iron transporter VIT plays a crucial role in iron detoxification in Toxoplasma gondii, regulating iron metabolism genes and increasing antioxidant activity. Iron detoxification is also important for parasite survival and virulence.
NATURE COMMUNICATIONS
(2023)
Review
Microbiology
Yolanda Rivera-Cuevas, Vern B. Carruthers
Summary: Intracellular pathogens interact with the ESCRT machinery of their hosts using short linear amino acid motifs similar to those used by ESCRTs to assemble on target membranes. They exploit this molecular mimicry to preserve their intracellular niche, gain resources, or egress from infected cells.
Article
Microbiology
Hilary Montano, Ramu Anandkrishnan, Vern B. B. Carruthers, Rajshekhar Y. Y. Gaji
Summary: Protein kinases of the protozoan parasite Toxoplasma gondii, especially TgTKL4, play important roles in regulating parasite motility, invasion, replication, egress, and survival within the host. Disruption of TgTKL4 results in replication and invasion defects, leading to altered parasite morphology and reduced virulence. The study provides insights into TgTKL4 as a fitness-determining factor for Toxoplasma propagation and pathogenesis.