Review
Cell Biology
Chinemerem P. Ogbu, Sourav Roy, Alex J. Vecchio
Summary: Claudins are integral membrane proteins that play a crucial role in cell-cell interactions by forming tight junctions. The bacterium Clostridium perfringens causes gastrointestinal disorders by targeting claudins with its enterotoxin (CpE), disrupting the barrier function of the gut. Understanding the structure and function of Claudin and CpE provides insights into the mechanisms underlying the disruption of tight junctions. This review summarizes the current progress in this field and highlights the importance of structural studies in developing therapeutic strategies.
Article
Food Science & Technology
Chinemerem P. Ogbu, Srajan Kapoor, Alex J. Vecchio
Summary: This study investigates the effects of trypsin on the structure of CpE and its role in CpE activation and oligomerization. The results reveal that trypsin cleavage alters the CpE structure, exposing normally hidden areas, and generates unique dimer interfaces that serve as oligomerization sites. The findings shed light on the role of trypsin in CpE function activation and oligomerization, and may inspire new approaches to inhibit CpE-based cytotoxicity through disrupting oligomerization.
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
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
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
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
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.
Article
Oncology
Jessica Pahle, Dennis Kobelt, Jutta Aumann, Diana Behrens, Ole Daberkow, Margarita Mokritzkij, Jorg Piontek, Ulrike Stein, Wolfgang Walther
Summary: A novel suicide gene therapy treatment based on Clostridium perfringens enterotoxin (CPE) has been developed to target claudin-3 and -4 (Cldn3/4) overexpressing pancreatic cancer cells, leading to rapid eradication and apoptotic/necrotic signaling. In vitro and in vivo studies demonstrate the selective toxicity and efficacy of this approach in treating pancreas carcinomas, with translational potential for clinical applications in combination with conventional chemotherapy.
Article
Microbiology
Mauricio A. Navarro, Jihong Li, Juliann Beingesser, Bruce A. McClane, Francisco A. Uzal
Summary: NanI can significantly enhance the activity of C. perfringens enterotoxin (CPE) in the presence of mucus, leading to increased cytotoxicity and damage to intestinal mucosa.
Article
Food Science & Technology
Thea Neumann, Maren Krueger, Jasmin Weisemann, Stefan Mahrhold, Daniel Stern, Martin B. Dorner, Cecile Feraudet-Tarisse, Christopher Poehlmann, Katharina Schulz, Ute Messelhaeusser, Dagmar Rimek, Frank Gessler, Thomas Elssner, Stephanie Simon, Andreas Rummel, Brigitte G. Dorner
Summary: The study successfully identified nine specific mAbs targeting CPE and showed their high affinity in detecting CPE. Through ELISAs, CPE can be detected specifically, which is useful for diagnosing diarrhea in clinical laboratories.
Article
Microbiology
Jihong Li, A. Bruce McClane
Summary: Clostridium perfringens type F strains, common causes of food poisoning, consistently carry the nanH sialidase gene, which is associated with NanH production during sporulation. The presence of NanH enhances the cytotoxicity of CPE for cells, potentially serving as an accessory virulence factor for type F food poisoning.
Article
Immunology
Jihong Li, Arhat Pradhan, Bruce A. McClane
Summary: Clostridium perfringens type F strains cause food poisoning by producing C. perfringens enterotoxin (CPE) during sporulation in the intestines. Most type F strains carry a chromosomal cpe gene (c-cpe strains). C. perfringens produces multiple sialidases, but some c-cpe strains only carry nanJ and nanH genes.
INFECTION AND IMMUNITY
(2023)
Article
Polymer Science
Dalsu Choi, Cheol Ho Lee, Han Bi Lee, Min Wook Lee, Seong Mu Jo
Summary: This research developed a simple and cost-effective method for fabricating electropositive membranes for efficient water filtration. The electropositive membranes are capable of filtering electronegative viruses and bacteria using electrostatic attraction, providing higher flux and enhanced filtration performance compared to conventional membranes. By modifying a SiO2/PVDF host membrane with electropositive boehmite nanoparticles, the researchers successfully created boehmite/SiO2/PVDF electropositive membranes using a simple dipping process. These membranes showed a comparable rejection rate and a higher water flux than a commercial filter, demonstrating their potential for water purification and disinfection.
Article
Biochemistry & Molecular Biology
Panpan Lin, Rongbang Tan, Ping Yu, Yanyu Li, Yuqian Mo, Wen Li, Jingjing Zhang
Summary: The blood-brain barrier is essential for protecting the central nervous system, but it also hinders efficient drug delivery. This study demonstrates that a mutated fragment of Clostridium perfringens enterotoxin can regulate the dynamics of the endothelial tight junction protein claudin-5 and influence blood-brain barrier permeability.
Article
Biotechnology & Applied Microbiology
Kengo Ueda, Kazuki Kawahara, Narumi Kimoto, Yusuke Yamaguchi, Kazuhiro Yamada, Hiroya Oki, Takuya Yoshida, Shigeaki Matsuda, Yuki Matsumoto, Daisuke Motooka, Kentaro Kawatsu, Tetsuya Iida, Shota Nakamura, Tadayasu Ohkubo, Shinya Yonogi
Summary: This study characterized the genomic epidemiology of bec-harbouring C. perfringens strains and highlighted the importance of pCP13-like plasmids for the dissemination of pathogenic strains. The plasmids were found to have a high gene transfer rate and the ability to integrate various foreign genes, including those associated with virulence.
Article
Immunology
Hiroyuki Abe, Shigeki Kamitani, Aya Fukui-Miyazaki, Naoaki Shinzawa, Keiji Nakamura, Yasuhiko Horiguchi
MICROBIOLOGY AND IMMUNOLOGY
(2015)
Article
Immunology
Sushmita Chakraborty, Bianca Kloos, Nina Roetz, Silke Schmidt, Tatjana Eigenbrod, Shigeki Kamitani, Katharina F. Kubatzky
Article
Microbiology
Aya Fukui-Miyazaki, Shigeki Kamitani, Masami Miyake, Yasuhiko Horiguchi
Article
Biochemistry & Molecular Biology
Joachim H. C. Orth, Ines Fester, Peter Siegert, Markus Weise, Ulrike Lanner, Shigeki Kamitani, Taro Tachibana, Brenda A. Wilson, Andreas Schlosser, Yasuhiko Horiguchi, Klaus Aktories
Article
Biochemistry & Molecular Biology
Shigeki Kamitani, Shinpei Ao, Hirono Toshima, Taro Tachibana, Makiko Hashimoto, Kengo Kitadokoro, Aya Fukui-Miyazaki, Hiroyuki Abe, Yasuhiko Horiguchi
Article
Microbiology
Masami Miyake, Sadatsugu Sakane, Chiho Kobayashi, Miyuki Hanajima-Ozawa, Aya Fukui, Shigeki Kamitani, Yasuhiko Horiguchi
FEMS MICROBIOLOGY LETTERS
(2008)
Article
Microbiology
Hiroe Ohnishi, Masami Miyake, Shigeki Kamitani, Yasuhiko Horiguchi
FEMS MICROBIOLOGY LETTERS
(2008)
Article
Biochemistry & Molecular Biology
Shigeki Kamitani, Kengo Kitadokoro, Masayuki Miyazawa, Hirono Toshima, Aya Fukui, Hiroyuki Abe, Masami Miyake, Yasuhiko Horiguchi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2010)
Article
Biochemistry & Molecular Biology
Kengo Kitadokoro, Kousuke Nishimura, Shigeki Kamitani, Aya Fukui-Miyazaki, Hirono Toshima, Hiroyuki Abe, Yoichi Kamata, Yoshiko Sugita-Konishi, Shigeki Yamamoto, Hajime Karatani, Yasuhiko Horiguchi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2011)
Article
Immunology
Takeshi Matsuzawa, Bae-Hoon Kim, Avinash R. Shenoy, Shigeki Kamitani, Masami Miyake, John D. MacMicking
JOURNAL OF IMMUNOLOGY
(2012)
Article
Immunology
Aya Fukui-Miyazaki, Shinya Ohnishi, Shigeki Kamitani, Hiroyuki Abe, Yasuhiko Horiguchi
MICROBIOLOGY AND IMMUNOLOGY
(2011)
Article
Biochemistry & Molecular Biology
Shigeki Kamitani, Katsutoshi Yamada, Shigenori Yamamoto, Yoshikazu Ishimoto, Takashi Ono, Akihiko Saiga, Kohji Hanasaki
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2012)
Article
Multidisciplinary Sciences
Kengo Kitadokoro, Shigeki Kamitani, Masayuki Miyazawa, Miyuki Hanajima-Ozawa, Aya Fukui, Masami Miyake, Yasuhiko Horiguchi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2007)
Article
Immunology
Miyuki Hanajima-Ozawa, Takeshi Matsuzawa, Aya Fukui, Shigeki Kamitani, Hiroe Ohnishi, Akio Abe, Yasuhiko Horiguchi, Masami Miyake
INFECTION AND IMMUNITY
(2007)