Article
Food Science & Technology
Andrey S. Selyunin, Karinel Nieves-Merced, Danyang Li, Stanton F. McHardy, Somshuvra Mukhopadhyay
Summary: Tamoxifen potently inhibits the trafficking of Shiga toxin 1 and 2 at the early endosome-to-Golgi step. This inhibitory effect is independent of its SERM property but relies on its weakly basic chemical nature, which alters endolysosomal pH and retromer recruitment. Tamoxifen exerts anti-STx2 activity by inhibiting retromer-dependent endosomal tubulation and sorting of STx2, highlighting its therapeutic potential for treating Shiga toxicosis.
Article
Pharmacology & Pharmacy
Zeinab Mohseni, Hamid Sedighian, Raheleh Halabian, Jafar Amani, Elham Behzadi, Abbas Ali Imani Fooladi
Summary: The study synthesized a novel antitumor candidate DT389-STXB fusion protein, which exhibited potential cytotoxicity against cancer cells, especially towards GB3-expressing breast cancer cells, demonstrating high affinity and dose-dependent cytotoxicity.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Hunseok Choi, Seonghyeon Son, Donghyun Lee, Jonghyun Bae, Eunyoung Seo, Dong Wook Kim, Eun Jin Kim
Summary: The study constructed new genes that can trigger the expression of TCP and CT in Vibrio cholerae, and induce antibody responses against TCP in animal models. However, the cholera toxin produced by these strains is secreted into the culture medium. To potentially apply in oral cholera vaccines, the researchers constructed V. cholerae strains that can express intracellular CTB under the control of the toxT-139F allele.
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Roberto M. Vidal, David A. Montero, Felipe Del Canto, Juan C. Salazar, Carolina Arellano, Alhejandra Alvarez, Nora L. Padola, Hernan Moscuzza, Analia Etcheverria, Daniel Fernandez, Victoria Velez, Mauro Garcia, Rocio Colello, Marcelo Sanz, Angel Onate
Summary: In this study, the safety and immunogenicity of a vaccine candidate against Shiga toxin-producing Escherichia coli (STEC) was evaluated. The vaccine, formulated with two chimeric proteins, was administered to pregnant cows in their third trimester of gestation. The results demonstrated that the vaccine is safe and immunogenic, suggesting the feasibility of vaccinating cows with it during late pregnancy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Mohsen Sadeghi, Frank Noe
Summary: Biomembrane remodeling is crucial for cellular trafficking, with membrane-binding proteins being key players. A coarse-grained model parametrized to reflect local curvatures and lateral dynamics of proteins was developed to study the formation and breakup of protein clusters on the membrane surface, demonstrating the role of protein flexibility and concentration in aggregation behavior.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Food Science & Technology
Alexander P. Gardner, Joseph T. Barbieri, Sabine Pellett
Summary: This study reveals that the potency of Botulinum neurotoxin serotype A is related to its stable co-localization on the plasma membrane. By exploring the structural elements, it is found that specific regions, termed MLD, R1, and R2, play independent roles in directing the co-localization of LC/A1 with SNAP-25. This research contributes to the understanding of the molecular basis of the high potency of BoNT/A1.
Article
Chemistry, Multidisciplinary
Luminita Claudia Miclea, Mona Mihailescu, Nicolae Tarba, Ana-Maria Brezoiu, Ana Maria Sandu, Raul-Augustin Mitran, Daniela Berger, Cristian Matei, Mihaela Georgeta Moisescu, Tudor Savopol
Summary: This study investigates the intracellular distribution of folate-conjugated mesoporous silica nanoparticles and demonstrates that the conjugation of folate increases the efficiency of nanoparticle uptake and promotes their preferential localization near the nucleus.
Article
Immunology
Silje N. Ramstad, Arne M. Taxt, Umaer Naseer, Yngvild Wasteson, Jorgen V. Bjornholt, Lin T. Brandal
Summary: The study found that some antibiotics can increase the production of Shiga toxin, while others do not. STEC O104:H4 was the serotype that exhibited the strongest response to antimicrobial exposure with an increase in stx2a transcription and Stx production.
MICROBIAL PATHOGENESIS
(2021)
Review
Nanoscience & Nanotechnology
Anand Saminathan, Matthew Zajac, Palapuravan Anees, Yamuna Krishnan
Summary: Intracellular organelles are subsystems within a cell that reflect the metabolic state of the cell, and biological pathways can be exploited to target exogenous cargo to specific organelles with nucleic acids as suitable delivery vehicles.
NATURE REVIEWS MATERIALS
(2022)
Article
Cell Biology
Jana Tomisch, Vincent Busse, Francesca Rosato, Olga N. Makshakova, Pavel Salavei, Anna-Sophia Kittel, Emilie Gillon, Levin Lataster, Anne Imberty, Ana Valeria Melendez, Winfried Roemer
Summary: The study demonstrates the selective targeting of Gb3-positive cancer cells using the StxB-scFv UCHT1 lectibody, which induces a killing effect of up to 80% on Gb3-overexpressing cancer cells in vitro. This highlights the potential of lectibodies and lectins in general for enhancing the efficacy of established cancer treatments through immunotherapeutic approaches.
Review
Food Science & Technology
Anne K. Kenworthy, Stefanie S. Schmieder, Krishnan Raghunathan, Ajit Tiwari, Ting Wang, Christopher V. Kelly, Wayne I. Lencer
Summary: CTxB is a stable homopentameric protein that tightly binds up to five GM1 glycosphingolipids, providing an important tool for studying membrane structure and dynamics.
Article
Pharmacology & Pharmacy
Daniel Tuse, Micaela Reeves, Joshua Royal, Krystal T. Hamorsky, Hanna Ng, Maria Arolfo, Carol Green, Abhishek Trigunaite, Toufan Parman, Goo Lee, Nobuyuki Matoba
Summary: This study established the pharmacokinetics, bioavailability, and acute safety of EPICERTIN in healthy and colitic mice and rats. It was found that EPICERTIN induced significant healing of damaged colonic epithelium when given at a specific dosage intrarectally.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Microbiology
Wouter J. C. Feitz, Romy Bouwmeester, Thea J. A. M. van der Velden, Susan Goorden, Christoph Licht, Lambert P. J. W. van den Heuvel, Nicole C. A. J. van de Kar
Summary: This study suggests that inhibiting the synthesis of Gb3 could be a potential therapeutic target for protecting against (further) endothelial damage caused by Stx in the future.
Review
Immunology
Tatiana M. Clemente, Rajendra K. Angara, Stacey D. Gilk
Summary: Obligate intracellular pathogens can either reside freely in the host cell cytoplasm or be confined in a membrane-bound vacuole. The pathogens in membrane-bound vacuoles are protected from the innate immune system and antimicrobial drugs, but they face challenges such as obtaining membrane components, maintaining a suitable microenvironment, acquiring essential nutrients from the host cell, and manipulating the host cell through a specialized secretion system.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Marco Lucchino, Anne Billet, Siau-Kun Bai, Estelle Dransart, Justine Hadjerci, Frederic Schmidt, Christian Wunder, Ludger Johannes
Summary: A sensitive and robust assay has been developed for quantifying the relative or absolute numbers of macromolecular drugs in the cytosol, facilitating the optimization of drug delivery vectors and enhancing understanding of the translocation process.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Cell Biology
Massiullah Shafaq-Zadah, Estelle Dransart, Ludger Johannes
CURRENT OPINION IN CELL BIOLOGY
(2020)
Article
Food Science & Technology
Annie Willysson, Anne-lie Stahl, Daniel Gillet, Julien Barbier, Jean-Christophe Cintrat, Valerie Chambon, Anne Billet, Ludger Johannes, Diana Karpman
Review
Biochemistry & Molecular Biology
Dhiraj Bhatia, Christian Wunder, Ludger Johannes
Summary: The field of DNA nanotechnology has branched out into structural, functional, and biologically oriented sub-branches, with a current trend of merging the functionality of DNA devices with the specificity of biomolecules to access a range of functions in biological systems.
Article
Cell Biology
Juan Jose Saez, Stephanie Dogniaux, Massiullah Shafaq-Zadah, Ludger Johannes, Claire Hivroz, Andres Ernesto Zucchetti
Summary: The paragraph discusses the important role of LAT in the signaling cascade induced by TCR activation, and its distribution and trafficking pathways in T cells upon activation. It shows that different proteins play specific roles in regulating the retrograde and anterograde transport of LAT during T cell activation.
Article
Biology
Alena Ivashenka, Christian Wunder, Valerie Chambon, Roger Sandhoff, Richard Jennemann, Estelle Dransart, Katrina Podsypanina, Berangere Lombard, Damarys Loew, Christophe Lamaze, Francoise Poirier, Hermann-Josef Groene, Ludger Johannes, Massiullah Shafaq-Zadah
Summary: Ivashenka et al. discovered that galectin-3 (Gal3) binding to lactotransferrin drives its transcytosis in enterocytes. Such trafficking is Gal3- and glycosphingolipid-dependent, and Gal3 is found in clathrin-independent carriers. These findings suggest that polarized trafficking across the intestinal barrier relies on this glycolipid and lectin (GL-Lect)-mediated endocytosis.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Marco Lucchino, Anne Billet, Siau-Kun Bai, Estelle Dransart, Justine Hadjerci, Frederic Schmidt, Christian Wunder, Ludger Johannes
Summary: A sensitive and robust assay has been developed for quantifying the relative or absolute numbers of macromolecular drugs in the cytosol, facilitating the optimization of drug delivery vectors and enhancing understanding of the translocation process.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Biochemistry & Molecular Biology
Coralie Croissant, Romain Carmeille, Charlotte Brevart, Anthony Bouter
Summary: Muscular dystrophies are genetic disorders characterized by weakening and loss of skeletal muscle mass. ANXA proteins are important for membrane repair in cells, and dysregulation of ANXA expression may impact the clinical severity of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Ludger Johannes
Summary: Biological membranes, as stable barriers that delimitate cells, are highly dynamic and enable lateral diffusion, transbilayer passage, and endocytic uptake. Lipids and complex sugars, the fundamental fabrics of membranes, are synthesized through complex biosynthetic enzymes, making them challenging to study using conventional reverse genetics. Organic synthesis offers new avenues for research in membrane glycobiology and its application in biomedicine.
Editorial Material
Cell Biology
Ludger Johannes, Cesar Augusto Valades-Cruz
Summary: This study reveals that invaginated clathrin-coated endocytic pits undergo a strong rotational twist prior to or concomitant with their detachment, which may depend on the 'pinchase' activity of dynamin.
NATURE CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Coralie Croissant, Celine Gounou, Flora Bouvet, Sisareuth Tan, Anthony Bouter
Summary: Defects in membrane repair contribute to the development of muscular dystrophies, and this study provides insights into the mechanism of membrane repair in healthy human skeletal muscle cells using correlative light and electron microscopy (CLEM). The results suggest that ANXA4 and ANXA6 are involved in sarcolemma remodeling and resealing, while ANXA1 and A2 contribute to membrane resealing by forming a lipid patch with intracellular vesicles.
Editorial Material
Food Science & Technology
Ludger Johannes
Article
Food Science & Technology
Eric Tartour, Ludger Johannes
Summary: Immunotherapy holds great promise for treating cancer and infectious diseases with high efficacy and minimal side effects. However, there is still a lack of mucosal vaccines to protect against tumors or infections affecting the upper airways or lungs. This review focuses on the B-subunit of Shiga toxin (STxB) as a potential mucosal vaccine candidate and compares it to other immunotherapy vectors. STxB has shown to induce humoral immunity and cellular immune responses, including CD4(+) and CD8(+) T lymphocytes, against tumor and viral antigens. Furthermore, STxB-based vaccines have demonstrated the ability to induce mucosal IgA and resident memory CD8(+) T cells when administered nasal route. The review also highlights the potential synergy between STxB-based vaccines and other therapeutic modalities in preclinical cancer models. The unique molecular characteristics of STxB, such as low immunogenicity and cross-species conservation of its target molecule, contribute to its competitive advantage among other dendritic cell targeting approaches. In conclusion, STxB appears as an original and innovative tool for the development of mucosal vaccines against infectious diseases and cancer.
Article
Cell Biology
Celine Gounou, Flora Bouvet, Benjamin Liet, Valerie Prouzet-Mauleon, Lena d'Agata, Etienne Harte, Francoise Argoul, Geraldine Siegfried, Richard Iggo, Abdel-Majid Khatib, Anthony Bouter
Summary: ANXA5 and ANXA6 are crucial components of the membrane repair machinery in MDA-MB-231 cells and are correlated with the invasiveness of breast cancer cells. High expression of ANXA5 and ANXA6 predicts poor prognosis in high-grade lung, gastric, and breast cancers. Genetic inhibition of ANXA5 and ANXA6 in zebrafish significantly reduces tumor cell dissemination.
BIOLOGY OF THE CELL
(2023)
Article
Cell Biology
Justine Hadjerci, Anne Billet, Pascal Kessler, Gilles Mourier, Marine Ghazarian, Anthony Gonzalez, Christian Wunder, Nesrine Mabrouk, Eric Tartour, Denis Servent, Ludger Johannes
Summary: Many molecular targets for cancer therapy are located in the cytosol, but therapeutic macromolecules generally cannot spontaneously translocate across membranes to reach these targets. To enhance cytosolic delivery, researchers have used Shiga toxin B-subunit (STxB) to deliver therapeutic principles to disease-relevant cells expressing its receptor, Gb3. By introducing unnatural amino acids and functionalizing them with hydrophobic entities, the membrane translocation of STxB was increased by a factor of 2.5, opening up new biomedical opportunities.
Article
Oncology
Marion Guerin, Fabienne Regnier, Maxime Thoreau, Lene Vimeux, Matthieu Benard, Estelle Dransart, Hweixian L. Penny, Ludger Johannes, Alain Trautmann, Nadege Bercovici
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)