Bacterial Enterotoxins: What’s New?

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 2257

Special Issue Editor


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Guest Editor
Department of Biology, Laurentian University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada
Interests: enterotoxin; pathogenesis; receptors; signaling; cell death
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Special Issue Information

Dear Colleagues,

It gives us great pleasure to invite you to participate in this Special Issue of Toxins, and we would like to thank you in advance for your contribution. We have witnessed significant advancements in the field of enterotoxins since their discovery; perhaps the spark that ignited curiosity and interest among researchers is the proposition by R. Koch, and others, in 1887 that cholera involved a toxin [Koch, R. 1887. Die Cholerabacillen; ihr Nachweis, ihre Lebensiegenshaften und die Art ihrer Verbreitung. Arbt. Kaiserl. Ges. (1887). 3:155.]. In the following decades, progress in this area was slow but subsequently greatly expanded with the development of biophysical methods. These methods, used in the study of toxins, have been key to our understanding of their 3D structures, dynamics, interactions with their receptors, and their functions. Just over a decade following the sequencing of the first protein (insulin, by Frederick Sanger in 1949), the 3D structures of the first proteins, myoglobin and hemoglobin, were reported in 1958 by Sir John Cowdery Kendrew and Max Perutz, respectively.

During this same period, another key technique was being developed. Isidor Isaac Rabi received the Nobel prize in physics in 1944 for the discovery of nuclear magnetic resonance (NMR), and shortly afterwards Edward Mills Purcell and Felix Bloch received the Nobel prize in physics in 1952 for developing NMR spectroscopy. Since then, NMR spectroscopy has advanced to include multidimensional NMR, paving the way to resolving complex NMR spectra and allowing for the elucidation of the 3D structures and dynamics of smaller proteins.

Today, we have extensive knowledge of a large number of toxins and their functions, especially those elaborated by pathogenic Escherichia coli, Shigella dysenteriae, Clostridium perfringens, and Clostridium difficile, to name a few examples. The list is extensive and we continue to discover new microbial toxins today.

In addition to unraveling the key aspects of enterotoxins, such as the interaction with their receptors, host cell penetration, as well as their specific actions on their final targets, there have been great developments in vaccine design and their use as adjuvants. More recent developments include the immunological aspect of enterotoxins. These include correlation between enterotoxins and negative heart function as well as other immunological disorders. This Special Issue of Toxins will provide the reader with a collection of recent research findings in this field, and your contribution is greatly appreciated.

Dr. Mazen Saleh
Guest Editor

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Keywords

  • enterotoxin
  • toxin function
  • AB-toxins
  • receptors
  • pathogenesis
  • vaccine

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Published Papers (1 paper)

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Research

16 pages, 3127 KiB  
Article
Extracellular Vesicle Inhibitors Enhance Cholix-Induced Cell Death via Regulation of the JNK-Dependent Pathway
by Kazuya Ozaki, Hiyo Nagahara, Asaka Kawamura, Takashi Ohgita, Sachika Higashi, Kohei Ogura, Hiroyasu Tsutsuki, Sunao Iyoda, Atsushi Yokotani, Toshiyuki Yamaji, Joel Moss and Kinnosuke Yahiro
Toxins 2024, 16(9), 380; https://doi.org/10.3390/toxins16090380 - 29 Aug 2024
Viewed by 1889
Abstract
Vibrio cholerae is an important foodborne pathogen. Cholix cytotoxin (Cholix), produced by V. cholerae, is a novel eukaryotic elongation factor 2 (eEF2) adenosine diphosphate ribosyltransferase that causes host cell death by inhibiting protein synthesis. However, the role of Cholix in the infectious [...] Read more.
Vibrio cholerae is an important foodborne pathogen. Cholix cytotoxin (Cholix), produced by V. cholerae, is a novel eukaryotic elongation factor 2 (eEF2) adenosine diphosphate ribosyltransferase that causes host cell death by inhibiting protein synthesis. However, the role of Cholix in the infectious diseases caused by V. cholerae remains unclear. Some bacterial cytotoxins are carried by host extracellular vesicles (EVs) and transferred to other cells. In this study, we investigated the effects of EV inhibitors and EV-regulating proteins on Cholix-induced hepatocyte death. We observed that Cholix-induced cell death was significantly enhanced in the presence of EV inhibitors (e.g., dimethyl amiloride, and desipramine) and Rab27a-knockdown cells, but it did not involve a sphingomyelin-dependent pathway. RNA sequencing analysis revealed that desipramine, imipramine, and EV inhibitors promoted the Cholix-activated c-Jun NH2-terminal kinase (JNK) pathway. Furthermore, JNK inhibition decreased desipramine-enhanced Cholix-induced poly (ADP-ribose) polymerase (PARP) cleavage. In addition, suppression of Apaf-1 by small interfering RNA further enhanced Cholix-induced PARP cleavage by desipramine. We identified a novel function of desipramine in which the stimulated JNK pathway promoted a mitochondria-independent cell death pathway by Cholix. Full article
(This article belongs to the Special Issue Bacterial Enterotoxins: What’s New?)
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