Article
Food Science & Technology
Masahiro Nagahama, Keiko Kobayashi, Sadayuki Ochi, Masaya Takehara
Summary: Clostridium botulinum C2 toxin requires lysosomal enzyme cathepsin B (CTSB) for effective cellular entry, with cysteine protease and aspartyl protease having different effects on cell rounding and extracellular ASMase activity induced by C2 toxin.
Review
Microbiology
Kathleen E. Orrell, Roman A. Melnyk
Summary: Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells, implicated as the primary virulence factors in various infections. Understanding the mechanism of LCT intoxication through recent structural work and toxin subtyping analysis is crucial for elucidating their role in infection and disease. Research on genomic discovery and characterization of LCT homologues provides valuable insights into this enigmatic family of toxins, offering perspectives on emerging questions and future research directions.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2021)
Article
Multidisciplinary Sciences
Akihiro Kawamoto, Tomohito Yamada, Toru Yoshida, Yusui Sato, Takayuki Kato, Hideaki Tsuge
Summary: Some bacteria have a toxin delivery system that transports enzymes into host cells. The bacterium Clostridioides difficile has a clinically important system with CDTa and CDTb proteins as therapeutic targets. The cryo-EM structure of CDTa bound to CDTb-pore was reported, revealing structural changes induced by CDTa binding and the involvement of an NSS-loop in substrate translocation. The dynamic information obtained provides insights for drug design against hypervirulent C. difficile strains.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Katharina Ernst, Judith Sailer, Maria Braune, Holger Barth
Summary: This study investigated the composition and mechanism of action of binary enterotoxins, as well as the protection of mammalian cells by inhibiting protein folding helper enzymes. The results suggest that simultaneous inhibition of these enzymes can effectively protect cells from intoxication, with a combination of inhibitors showing enhanced effects compared to individual inhibitors.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(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
Food Science & Technology
Jinfang Jia, Maria Braune-Yan, Stefanie Lietz, Mary Wahba, Arto T. Pulliainen, Holger Barth, Katharina Ernst
Summary: Bordetella pertussis toxin (PT) and Clostridium botulinum C2 toxin are ADP-ribosylating toxins that require cellular chaperones Hsp90 and Hsp70, cyclophilins, and FK506-binding proteins for translocation. Inhibition of chaperone activities can protect cells from PT and C2 intoxication. Domperidone, a dopamine receptor antagonist, was found to inhibit Hsp70 activity and protect cells from intoxication. Domperidone inhibits enzyme subunit translocation and reduces toxin uptake, making it a potential therapeutic agent for diseases caused by bacterial toxins that require Hsp70.
Review
Microbiology
Shuowei Cai, Raj Kumar, Bal Ram Singh
Summary: Gram-positive bacteria are ancient organisms that produce toxins to manipulate the host and lead to diseases. Clostridial neurotoxins, like other bacterial toxins, use flexible structures to trigger their activity. Understanding these structures is vital for designing antidotes against bacterial toxins.
Article
Pharmacology & Pharmacy
Julia Eisele, Simone Schreiner, Joscha Borho, Stephan Fischer, Sebastian Heber, Sascha Endres, Maximilian Fellermann, Lisa Wohlgemuth, Markus Huber-Lang, Giorgio Fois, Michael Fauler, Manfred Frick, Holger Barth
Summary: The binary C2 toxin of Clostridium botulinum consists of two non-linked proteins, C2I and C2II. C2IIa enters the cytosol through receptor-mediated endocytosis and causes morphological changes in cells.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kathleen E. Orrell, Roman A. Melnyk
Summary: Large clostridial toxins (LCTs) are a family of disease-causing proteins characterized by their large size and conserved multidomain architectures; the discovery of LCT-like T domains in diverse bacteria has provided new insights into LCT translocation.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Review
Gastroenterology & Hepatology
Salvador Lopez-Cardenas, Eva Torres-Martos, Juan Mora-Delgado, Juan Manuel Sanchez-Calvo, Marta Santos-Pena, Angel Zapata Lopez, Maria Dolores Lopez-Prieto, Salvador Perez-Cortes, Juan Carlos Alados
Summary: The study revealed that patients with detected presence of TcdB and CDT in feces exhibited greater disease severity and higher recurrence rates compared to those without detection. Simultaneous detection of both markers had a stronger impact on prognosis in cases of CDI.
Article
Food Science & Technology
Simab Kanwal, Shalini Abeysinghe, Monrudee Srisaisup, Panadda Boonserm
Summary: The binary toxin produced by Lysinibacillus sphaericus, containing BinA and BinB, shows high toxicity against mosquito larvae and cytotoxicity against HepG2 cells but not Hs68 cells. The study suggests the potential development of Bin toxin as an anticancer agent or a selective delivery vehicle for anticancer agents targeting mitochondria in human cancer cells.
Article
Microbiology
Yoshihiko Sakaguchi, Keiko Kobayashi, Masaya Takehara, Masahiro Nagahama
Summary: In this study, it was found that acid sphingomyelinase promotes the internalization of epsilon-toxin in MDCK cells. Blocking acid sphingomyelinase and exocytosis of lysosomes inhibited epsilon-toxin-induced vacuole formation. RNAi-mediated attenuation of acid sphingomyelinase blocked epsilon-toxin-induced vacuolation.
Article
Multidisciplinary Sciences
L. Nie, A. C. Nusantara, V. G. Damle, R. Sharmin, E. P. P. Evans, S. R. Hemelaar, K. J. van der Laan, R. Li, F. P. Perona Martinez, T. Vedelaar, M. Chipaux, R. Schirhagl
Summary: Relaxometry measurement inherited from diamond magnetometry can be used to detect free radicals in living cells with subcellular resolution. This quantum sensing technique based on defects in diamond allows nanoscale magnetic resonance measurements to detect metabolic activity in mitochondria.
Article
Microbiology
Angela Saadat, Stephen B. Melville
Summary: Researchers have identified a novel family of holin-like proteins that can act as a system for protein secretion in some cases. This discovery sheds light on the mechanism by which large clostridial toxins are secreted and may provide insights into how proteins fold in the cytoplasm.
JOURNAL OF BACTERIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Samrat Mazumdar, Deepak Chitkara, Anupama Mittal
Summary: The beneficial or deleterious effects of nanomedicines are influenced by their complex interactions with intracellular pathways and their subcellular fate. Manipulating the physicochemical attributes of nanocarriers can direct nanoparticles towards specific sub-cellular organelles, affecting cellular internalization and enhancing intracellular uptake via specific endocytic pathways.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Biochemistry & Molecular Biology
Soshi Seike, Masaya Takehara, Keiko Kobayashi, Masahiro Nagahama
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2016)
Article
Pharmacology & Pharmacy
Masaya Takehara, Teruhisa Takagishi, Soshi Seike, Kyohei Oishi, Yoshino Fujihara, Kazuaki Miyamoto, Keiko Kobayashi, Masahiro Nagahama
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2016)
Article
Biochemistry & Molecular Biology
Soshi Seike, Masaya Takehara, Teruhisa Takagishi, Kazuaki Miyamoto, Keiko Kobayashi, Masahiro Nagahama
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2018)
Article
Multidisciplinary Sciences
Soshi Seike, Kazuaki Miyamoto, Keiko Kobayashi, Masaya Takehara, Masahiro Nagahama
Article
Multidisciplinary Sciences
Hidetomo Kobayashi, Tadamune Otsubo, Fumiteru Teraoka, Kiyoshi Ikeda, Soshi Seike, Eizo Takahashi, Keinosuke Okamoto, Toru Yoshida, Hideaki Tsuge, Hiroyasu Yamanaka
Article
Multidisciplinary Sciences
Teruhisa Takagishi, Masaya Takehara, Soshi Seike, Kazuaki Miyamoto, Keiko Kobayashi, Masahiro Nagahama
SCIENTIFIC REPORTS
(2017)
Article
Food Science & Technology
Soshi Seike, Masaya Takehara, Keiko Kobayashi, Masahiro Nagahama
Article
Multidisciplinary Sciences
Hidetomo Kobayashi, Soshi Seike, Masafumi Yamaguchi, Mitsunobu Ueda, Eizo Takahashi, Keinosuke Okamoto, Hiroyasu Yamanaka
Article
Food Science & Technology
Masahiro Nagahama, Soshi Seike, Sadayuki Ochi, Keiko Kobayashi, Masaya Takehara
Article
Microbiology
Soshi Seike, Hidetomo Kobayashi, Mitsunobu Ueda, Eizo Takahashi, Keinosuke Okamoto, Hiroyasu Yamanaka
Summary: This study is the first to examine the in vitro formation and components of the biofilm of several Aeromonas clinical and environmental strains, revealing that the biofilms contain polysaccharides, extracellular nucleic acids, and proteins. Among these components, some proteins in the Aeromonas biofilms may affect biofilm formation. Furthermore, the release of outer membrane vesicles by Aeromonas strains was found to be closely related to biofilm formation.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Mitsunobu Ueda, Hidetomo Kobayashi, Soshi Seike, Eizo Takahashi, Keinosuke Okamoto, Hiroyasu Yamanaka
Summary: Aeromonas sobria, a Gram-negative pathogen causing food-borne illness, opportunistically leads to severe extraintestinal diseases in immunocompromised patients and the elderly. It can disrupt the barrier function of the intestinal epithelium by destroying tight junctions, potentially aiding the invasion of pathogens into deep sites in the human body.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biology
Masaya Takehara, Soshi Seike, Yuuta Sonobe, Hiroto Bandou, Saki Yokoyama, Teruhisa Takagishi, Kazuaki Miyamoto, Keiko Kobayashi, Masahiro Nagahama
COMMUNICATIONS BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Masaya Takehara, Soshi Seike, Teruhisa Takagishi, Keiko Kobayashi, Masahiro Nagahama
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2017)
Article
Immunology
Masahiro Nagahama, Masaya Takehara, Teruhisa Takagishi, Soshi Seike, Kazuaki Miyamoto, Keiko Kobayashi
INFECTION AND IMMUNITY
(2017)
