Article
Biochemistry & Molecular Biology
Julia Bruggisser, Ioan Iacovache, Samuel C. Musson, Matteo T. Degiacomi, Horst Posthaus, Benoit Zuber
Summary: This study describes the structure of Clostridium perfringens beta-toxin (CPB) and its formation of an octameric pore complex with unique structural features. The research also identifies CPB as a member of a new subclass of the hemolysin-like family. Additionally, the study demonstrates that the structure of the pore can be modified without affecting its pore-forming ability, making it attractive for macromolecule sensing and nanotechnology. The cryo-electron microscopy structure of the CPB octameric pore will contribute to future developments in nanotechnology and basic research.
Article
Medicine, Research & Experimental
Yinghua Ma, David Sannino, Jennifer R. Linden, Sylvia Haigh, Baohua Zhao, John B. Grigg, Paul Zumbo, Friederike Duendar, Daniel Butler, Caterina P. Profaci, Kiel Telesford, Paige N. Winokur, Kareem R. Rumah, Susan A. Gauthier, Vincent A. Fischetti, Bruce A. McClane, Francisco A. Uzal, Lily Zexter, Michael Mazzucco, Richard Rudick, David Danko, Evan Balmuth, Nancy Nealon, Jai Perumal, Ulrike Kaunzner, Ilana L. Brito, Zhengming Chen, Jenny Z. Xiang, Doron Betel, Richard Daneman, Gregory F. Sonnenberg, Christopher E. Mason, Timothy Vartanian
Summary: Multiple sclerosis (MS), a complex disease of the CNS, has been linked to gut dysbiosis. This study found that individuals with MS were more likely to have epsilon toxin-producing strains of C. perfringens in their gut microbiomes compared to healthy controls. These strains were able to produce functional epsilon toxin and had genetic characteristics similar to highly conjugative plasmids. In an animal model of MS, epsilon toxin could substitute for pertussis toxin and induced demyelination in various regions of the CNS, similar to lesions seen in MS patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud
Summary: The study reveals the molecular and structural basis of how CpE targets susceptible claudins, as well as differences in the primary CpE receptors in mice and humans due to sequence changes in the target motif.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Food Science & Technology
Masahiro Nagahama, Keiko Kobayashi, Masaya Takehara
Summary: The study found that lysosomal proteases cathepsin B and L facilitate the internalization of iota-toxin by activating ASMase, indicating their role in the cytotoxicity caused by the toxin.
Article
Microbiology
Archana Shrestha, Mauricio A. Navarro, Juliann Beingesser, Anibal G. Armien, Francisco A. Uzal, Bruce A. McCiane
Summary: Clostridium perfringens enterotoxin (CPE) causes lethal enterotoxemia when absorbed into the bloodstream, with full CPE-induced cytotoxicity leading to rapid permeability alterations and lethality. Testing recombinant CPE (rCPE) variants showed that receptor binding-capable, noncytotoxic rCPE cause slow-developing permeability effects, highlighting the importance of cytotoxicity for rapid permeability changes and lethality.
Article
Chemistry, Multidisciplinary
Man Kyu Shim, Jinhee Na, In Kyung Cho, Eun Hyang Jang, Jooho Park, Sangmin Lee, Jong-Ho Kim
Summary: The study developed a claudin-4-targeting drug carrier that efficiently accumulated in pancreatic cancer tissues, suppressed tumor growth with minimal toxicity to normal tissues. This claudin-4-targeting drug carrier may represent a promising new approach for treating pancreatic cancer.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Food Science & Technology
Jihong Li, Eric Mi, Arhat Pradhan, Bruce A. McClane
Summary: This study investigated the influence of NanR on c-cpe strains. In sporulation medium, the nanR null mutants showed lower sialidase activity, sporulation, and CPE production. In vegetative medium, the nanR null mutants produced more spores. These results suggest that NanR plays a crucial role in the regulation of c-cpe strains.
Review
Biochemistry & Molecular Biology
John W. Finnie, Francisco A. Uzal
Summary: Clostridium perfringens type D epsilon toxin (ETX) causes severe neurological disease in ruminant livestock and is of worldwide distribution. The toxin can reach the brain through the bloodstream, leading to neurologic syndromes. ETX is also listed as a potential bioterrorism agent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Luis F. Soto, Ana C. Romani, Gabriel Jimenez-Avalos, Yshoner Silva, Carla M. Ordinola-Ramirez, Rainer M. Lopez Lapa, David Requena
Summary: This study computationally screened the whole proteome of Clostridium perfringens and identified highly immunogenic proteins, domains, and epitopes. They found potential recombinant vaccine candidates, a potential sub-unit vaccine, and designed a multi-epitope protein. These findings are important for the development of safe and effective vaccines against C. perfringens infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Food Science & Technology
Basma Tarek, Julia Bruggisser, Filippo Cattalani, Horst Posthaus
Summary: Beta toxin (CPB) is a toxin produced by Clostridium perfringens type C that targets intestinal endothelial cells by interacting with the membrane protein CD31. This study confirms CD31 as the receptor of CPB on human endothelial and monocytic cells, explaining the cell type specificity of CPB observed in vitro and in vivo.
Review
Oncology
Amita R. Banga, Peace Odiase, Kartik Rachakonda, Amar P. Garg, Samuel E. Adunyah, Girish Rachakonda
Summary: This article discusses the potential value of the interaction between Clostridium perfringens Enterotoxin (CPE) and Claudin-4 in the treatment of breast cancer metastasis to the brain, and introduces the important role of Claudin-4 in cell trafficking and disease development.
Review
Agriculture, Dairy & Animal Science
Francisco A. Uzal, Federico Giannitti, Javier Asin
Summary: Yellow lamb disease is a poorly understood condition in young sheep caused by certain strains of Clostridium perfringens type A. It is characterized by hemolysis, jaundice, and anemia. Diagnosis of the disease is challenging due to the presence of the microorganism in the intestines of healthy sheep. There is currently no specific vaccine for yellow lamb disease.
Article
Multidisciplinary Sciences
Jie Li, Xiaoyu Huang, Kaihui Xie, Juanli Zhang, Jiaojiao Yang, Zunqiang Yan, Shuangbao Gun
Summary: S100A9 plays an important role in C. perfringens type C-induced infectious diarrhea. Overexpression of S100A9 exacerbates cell damage and inflammatory response, inhibits cell proliferation, and disrupts cell-cell tight junctions. In contrast, inhibition of S100A9 expression alleviates inflammatory injury caused by infectious diarrhea.
Article
Immunology
Lore Van Damme, Natasja Cox, Chana Callens, Michelle Dargatz, Monika Fluegel, Sarah Hark, Frank Thiemann, Stefan Pelzer, Freddy Haesebrouck, Richard Ducatelle, Filip Van Immerseel, Evy Goossens
Summary: Clostridium perfringens produces ECM-degrading enzymes that play a role in avian necrotic enteritis. Different variants of the colA gene encoding collagenase were identified, with some variants linked to necrotic enteritis strains. Truncated collagenases may contribute to the pathology of necrotic enteritis by degrading collagen type IV in the intestinal villi.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Food Science & Technology
Skye Marshall, Beth McGill, Helen Morcrette, C. Peter Winlove, Catalin Chimerel, Peter G. Petrov, Monika Bokori-Brown
Summary: This study investigates the activity of Clostridium perfringens epsilon toxin (Etx) in different cell lines and lipid environments. The results show that the efficiency of Etx binding to cells is species-specific and influenced by surface-exposed tyrosine residues, while the pore-forming ability of Etx is affected by both the cell and lipid environment.