Gram Positive Toxins Producing Organisms, 2nd Edition

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 8146

Special Issue Editors


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Guest Editor
Division of Microbiology, Office of Regulatory Science, CFSAN/US Food and Drug Administration, College Park, MD 20740, USA
Interests: select agent research; toxins; bacteria; gram positive

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Guest Editor
IHRC, Inc., 2 Ravinia Drive, Suite 1200, Atlanta, GA 30346, USA
Interests: all aspect of select agent research; gram positive bacterial and other toxins

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue: "Gram Positive Toxins Producing Organisms".

Many bacteria produce toxins that are essential in the medical field. Vaccines have been developed for some toxin-mediated diseases (e.g., tetanus, diphtheria) and continue to play a significant role in the prevention of disease. Over the past few decades, great strides have been made in our understanding of the structure and function of bacterial toxins and their role in diseases. These advances reflect the productive interactions of disciplines, such as protein chemistry and crystallography, molecular genetics, molecular biology, genomics, immunology, neurobiology, pharmacology, and biophysics. Remarkable progress has been made in the elucidation of the molecular mechanisms of a wide range of toxins with increasing numbers found to have enzymatic activities, including those that ADP-ribosylate (e.g., diphtheria toxin) and glycosylate novel targets, as well as Zn-proteinases with exquisite specificities (e.g., botulinum A neurotoxin and SNAP-25).    The host immune system is not only the primary defense against colonization and sometimes invasion by toxigenic bacteria, but it also constitutes a major target for bacterial toxins that can act either directly via cytotoxicity to immune effector cells, or indirectly via the deregulation of cytokine production.

Toxin genes and other virulence determinants are frequently encoded by mobile genetic elements, which are located on pathogenicity islands and/or on mobilizable genetic elements, such as plasmids, transposons, and bacteriophages. These genetic elements have the capacity to be spread by horizontal gene transfer, contributing to the rapid evolution of bacterial pathogens as the rearrangement, excision and acquisition of large genomic regions creates new pathogenic variants. The occurrence of toxin-encoding genes on various interdepending genetic elements, their ability to delete from and integrate into chromosomal DNA and the existence of toxin families among a wide variety of bacterial species demonstrate that toxigenic pathogen evolution is connected to the transfer of foreign DNA harboring toxin determinants.

The aim of this Special Issue is to provide a collection of articles that highlights research on bacterial toxins. The editors chose to focus this Special Issue on Gram-positive bacterial toxins. We welcome submissions reflecting all aspects of toxin research from applied (novel diagnostics, countermeasures, vaccines) to more basic research areas related to the biology of the toxin, genomics, and pathogenesis.  Gram-positive toxins include, but are not limited to, tetanus toxin, botulinum toxins, staphylococcal toxins, diphtheria toxin, streptococcal toxins, Listeria toxin, anthrax toxins, Bacillus cereus toxins, pneumolysin, enterococcal toxins, and other clostridial toxins (e.g., perfringolysin O). Each of these toxins has a unique story to tell but needs a storyteller. We hope you will be able to contribute to this Special Issue on Gram-positive toxins.

Dr. Shashi Sharma
Dr. Stephen A. Morse
Dr. Sabine Pellett
Guest Editors

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Published Papers (4 papers)

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Editorial

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6 pages, 210 KiB  
Editorial
Special Issue: Gram-Positive Bacterial Toxins
by Shashi Sharma, Sabine Pellett and Stephen A. Morse
Microorganisms 2023, 11(8), 2054; https://doi.org/10.3390/microorganisms11082054 - 10 Aug 2023
Cited by 2 | Viewed by 2459
Abstract
The Gram stain classifies most bacteria into one of two groups, Gram-negative or Gram-positive, based on the composition of their cell walls [...] Full article
(This article belongs to the Special Issue Gram Positive Toxins Producing Organisms, 2nd Edition)

Research

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17 pages, 2218 KiB  
Article
Expression of Recombinant Clostridial Neurotoxin by C. tetani
by Brieana M. Gregg, Sonal Gupta, William H. Tepp and Sabine Pellett
Microorganisms 2024, 12(12), 2611; https://doi.org/10.3390/microorganisms12122611 - 17 Dec 2024
Viewed by 892
Abstract
Tetanus neurotoxins (TeNT) and botulinum neurotoxins (BoNTs) are closely related ~150 kDa protein toxins that together comprise the group of clostridial neurotoxins (CNTs) expressed by various species of Clostridia. While TeNT is expressed as a single polypeptide, BoNTs are always produced alongside [...] Read more.
Tetanus neurotoxins (TeNT) and botulinum neurotoxins (BoNTs) are closely related ~150 kDa protein toxins that together comprise the group of clostridial neurotoxins (CNTs) expressed by various species of Clostridia. While TeNT is expressed as a single polypeptide, BoNTs are always produced alongside multiple non-toxic proteins that form a stabilizing complex with BoNT and are encoded in a conserved toxin gene cluster. It is unknown how tent evolved without a similar gene cluster and why complex-free TeNT is secreted as a stable and soluble protein by C. tetani, whereas complexing proteins appear to be essential for BoNT stability in culture supernatants of C. botulinum. To assess whether the stability of TeNT is due to an innate property of the toxin or is a result of C. tetani’s intra- and extra-cellular environment, both TeNT and complex-free BoNT/A1ERY were expressed recombinantly in atoxic C. tetani and analyzed for expression and stability. The strong clostridial ferredoxin (fdx) promotor resulted in the expression of recombinant TeNT at greater levels and earlier time points than endogenously produced TeNT. Recombinant BoNT/A1ERY was similarly expressed by atoxic C. tetani, although partial degradation was observed. The rBoNT/A1ERY produced in C. tetani was also partially proteolytically processed to the dichain form. Investigations of bacterial growth media and pH conditions found that the stability of rTeNT and rBoNT/A1ERY in spent media of C. tetani or C. botulinum was affected by growth media but not by pH. These data indicate that the distinct metabolism of C. tetani or C. botulinum under various growth conditions is a primary factor in creating a more or less favorable environment for complex-free CNT stability. Full article
(This article belongs to the Special Issue Gram Positive Toxins Producing Organisms, 2nd Edition)
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13 pages, 1973 KiB  
Article
Regulation of Staphylococcal Enterotoxin-Induced Inflammation in Spleen Cells from Diabetic Mice by Polyphenols
by Yuko Shimamura, Rina Noaki, Yukino Oura, Kenya Ichikawa, Toshiyuki Kan and Shuichi Masuda
Microorganisms 2023, 11(4), 1039; https://doi.org/10.3390/microorganisms11041039 - 15 Apr 2023
Cited by 1 | Viewed by 1642
Abstract
Patients with diabetes are known to be more susceptible to infections following the establishment of Staphylococcus aureus in their nasal passages and on their skin. The present study evaluated the effects of staphylococcal enterotoxin A (SEA) on the immune responses of spleen cells [...] Read more.
Patients with diabetes are known to be more susceptible to infections following the establishment of Staphylococcus aureus in their nasal passages and on their skin. The present study evaluated the effects of staphylococcal enterotoxin A (SEA) on the immune responses of spleen cells derived from diabetic mice, and examined the effects of polyphenols, catechins, and nobiletin on inflammation-related gene expression associated with the immune response. (−)-Epigallocatechin gallate (EGCG), possessing hydroxyl groups, interacted with SEA, whereas nobiletin, possessing methyl groups, did not interact with SEA. The exposure of spleen cells derived from diabetic mice to SEA enhanced the expression of interferon gamma, suppressor of cytokine signaling 1, signal transducer and activator of transcription 3, interferon-induced transmembrane protein 3, Janus kinase 2, and interferon regulatory factor 3, suggesting that SEA sensitivity is variable in the development of diabetes. Both EGCG and nobiletin changed the expression of genes related to SEA-induced inflammation in spleen cells, suggesting that they inhibit inflammation through different mechanisms. These results may lead to a better understanding of the SEA-induced inflammatory response during diabetogenesis, and the establishment of methods to control these effects with polyphenols. Full article
(This article belongs to the Special Issue Gram Positive Toxins Producing Organisms, 2nd Edition)
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Review

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16 pages, 1667 KiB  
Review
Depression Treatment: Is There a Role for Botulinum Toxin Type A?
by Carmen Rodríguez-Cerdeira and Westley Eckhardt
Microorganisms 2024, 12(12), 2615; https://doi.org/10.3390/microorganisms12122615 - 17 Dec 2024
Viewed by 548
Abstract
This study aimed to determine whether botulinum toxin type A injected into the muscles of the upper third of the face has antidepressant effects in patients diagnosed with depression. Studies seeking a relationship between botulinum toxin type A and its antidepressant effects were [...] Read more.
This study aimed to determine whether botulinum toxin type A injected into the muscles of the upper third of the face has antidepressant effects in patients diagnosed with depression. Studies seeking a relationship between botulinum toxin type A and its antidepressant effects were considered in this review. All studies concluded that the facial expression muscles present positive feedback to the brain and enhance mood states. Botulinum toxin when applied to the corrugator and procerus muscles has an antidepressant effect. Full article
(This article belongs to the Special Issue Gram Positive Toxins Producing Organisms, 2nd Edition)
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