Editorial

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5 pages, 199 KiB

Open AccessEditorial

Toxins, Pathogenicity, Anti-Toxins, a Bicentennial Contribution

by Michel R. Popoff and Daniel Ladant

Toxins 2024, 16(2), 97; https://doi.org/10.3390/toxins16020097 - 10 Feb 2024

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The bicentenary of Louis Pasteur’s birth raises the opportunity to revisit the activity and influence of L [...] Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

Review

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29 pages, 20225 KiB

Open AccessFeature PaperReview

Bacillus anthracis, “la maladie du charbon”, Toxins, and Institut Pasteur

by Pierre L. Goossens

Toxins 2024, 16(2), 66; https://doi.org/10.3390/toxins16020066 - 26 Jan 2024

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Abstract

Institut Pasteur and Bacillus anthracis have enjoyed a relationship lasting almost 120 years, starting from its foundation and the pioneering work of Louis Pasteur in the nascent fields of microbiology and vaccination, and blooming after 1986 following the molecular biology/genetic revolution. This contribution [...] Read more.

Institut Pasteur and Bacillus anthracis have enjoyed a relationship lasting almost 120 years, starting from its foundation and the pioneering work of Louis Pasteur in the nascent fields of microbiology and vaccination, and blooming after 1986 following the molecular biology/genetic revolution. This contribution will give a historical overview of these two research eras, taking advantage of the archives conserved at Institut Pasteur. The first era mainly focused on the production, characterisation, surveillance and improvement of veterinary anthrax vaccines; the concepts and technologies with which to reach a deep understanding of this research field were not yet available. The second period saw a new era of B. anthracis research at Institut Pasteur, with the anthrax laboratory developing a multi-disciplinary approach, ranging from structural analysis, biochemistry, genetic expression, and regulation to bacterial-host cell interactions, in vivo pathogenicity, and therapy development; this led to the comprehensive unravelling of many facets of this toxi-infection. B. anthracis may exemplify some general points on how science is performed in a given society at a given time and how a scientific research domain evolves. A striking illustration can be seen in the additive layers of regulations that were implemented from the beginning of the 21st century and their impact on B. anthracis research. B. anthracis and anthrax are complex systems that raise many valuable questions regarding basic research. One may hope that B. anthracis research will be re-initiated under favourable circumstances later at Institut Pasteur. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

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17 pages, 2191 KiB

Open AccessReview

Animal Toxins: A Historical Outlook at the Institut Pasteur of Paris

by Michel R. Popoff, Grazyna Faure, Sandra Legout and Daniel Ladant

Toxins 2023, 15(7), 462; https://doi.org/10.3390/toxins15070462 - 19 Jul 2023

Cited by 1 | Viewed by 1655

Abstract

Humans have faced poisonous animals since the most ancient times. It is recognized that certain animals, like specific plants, produce toxic substances that can be lethal, but that can also have therapeutic or psychoactive effects. The use of the term “venom”, which initially [...] Read more.

Humans have faced poisonous animals since the most ancient times. It is recognized that certain animals, like specific plants, produce toxic substances that can be lethal, but that can also have therapeutic or psychoactive effects. The use of the term “venom”, which initially designated a poison, remedy, or magic drug, is now confined to animal poisons delivered by biting. Following Louis Pasteur’s work on pathogenic microorganisms, it was hypothesized that venoms could be related to bacterial toxins and that the process of pathogenicity attenuation could be applied to venoms for the prevention and treatment of envenomation. Cesaire Phisalix and Gabriel Bertrand from the National Museum of Natural History as well as Albert Calmette from the Institut Pasteur in Paris were pioneers in the development of antivenomous serotherapy. Gaston Ramon refined the process of venom attenuation for the immunization of horses using a formalin treatment method that was successful for diphtheria and tetanus toxins. This paved the way for the production of antivenomous sera at the Institut Pasteur, as well as for research on venom constituents and the characterization of their biological activities. The specific activities of certain venom components, such as those involved in blood coagulation or the regulation of chloride ion channels, raises the possibility of developing novel therapeutic drugs that could serve as anticoagulants or as a treatment for cystic fibrosis, for example. Scientists of the Institut Pasteur of Paris have significantly contributed to the study of snake venoms, a topic that is reported in this review. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

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15 pages, 814 KiB

Open AccessReview

Modulation of Airway Expression of the Host Bactericidal Enzyme, sPLA2-IIA, by Bacterial Toxins

by Yongzheng Wu, Erwan Pernet and Lhousseine Touqui

Toxins 2023, 15(7), 440; https://doi.org/10.3390/toxins15070440 - 03 Jul 2023

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Abstract

Host molecules with antimicrobial properties belong to a large family of mediators including type-IIA secreted phospholipase A2 (sPLA2-IIA). The latter is a potent bactericidal agent with high selectivity against Gram-positive bacteria, but it may also play a role in modulating the host inflammatory [...] Read more.

Host molecules with antimicrobial properties belong to a large family of mediators including type-IIA secreted phospholipase A2 (sPLA2-IIA). The latter is a potent bactericidal agent with high selectivity against Gram-positive bacteria, but it may also play a role in modulating the host inflammatory response. However, several pathogen-associated molecular patterns (PAMPs) or toxins produced by pathogenic bacteria can modulate the levels of sPLA2-IIA by either inducing or inhibiting its expression in host cells. Thus, the final sPLA2-IIA concentration during the infection process is determined by the orchestration between the levels of toxins that stimulate and those that downregulate the expression of this enzyme. The stimulation of sPLA2-IIA expression is a process that participates in the clearance of invading bacteria, while inhibition of this expression highlights a mechanism by which certain bacteria can subvert the immune response and invade the host. Here, we will review the major functions of sPLA2-IIA in the airways and the role of bacterial toxins in modulating the expression of this enzyme. We will also summarize the major mechanisms involved in this modulation and the potential consequences for the pulmonary host response to bacterial infection. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

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10 pages, 733 KiB

Open AccessReview

Regulation of Clostridial Toxin Gene Expression: A Pasteurian Tradition

by Bruno Dupuy

Toxins 2023, 15(7), 413; https://doi.org/10.3390/toxins15070413 - 26 Jun 2023

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Abstract

The alarming symptoms attributed to several potent clostridial toxins enabled the early identification of the causative agent of tetanus, botulism, and gas gangrene diseases, which belongs to the most famous species of pathogenic clostridia. Although Clostridioides difficile was identified early in the 20th [...] Read more.

The alarming symptoms attributed to several potent clostridial toxins enabled the early identification of the causative agent of tetanus, botulism, and gas gangrene diseases, which belongs to the most famous species of pathogenic clostridia. Although Clostridioides difficile was identified early in the 20th century as producing important toxins, it was identified only 40 years later as the causative agent of important nosocomial diseases upon the advent of antibiotic therapies in hospital settings. Today, C. difficile is a leading public health issue, as it is the major cause of antibiotic-associated diarrhea in adults. In particular, severe symptoms within the spectrum of C. difficile infections are directly related to the levels of toxins produced in the host. This highlights the importance of understanding the regulation of toxin synthesis in the pathogenicity process of C. difficile, whose regulatory factors in response to the gut environment were first identified at the Institut Pasteur. Subsequently, the work of other groups in the field contributed to further deciphering the complex mechanisms controlling toxin production triggered by the intestinal dysbiosis states during infection. This review summarizes the Pasteurian contribution to clostridial toxin regulation studies. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

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13 pages, 1097 KiB

Open AccessReview

Cyanotoxins and Other Bioactive Compounds from the Pasteur Cultures of Cyanobacteria (PCC)

by Muriel Gugger, Anne Boullié and Thierry Laurent

Toxins 2023, 15(6), 388; https://doi.org/10.3390/toxins15060388 - 09 Jun 2023

Cited by 2 | Viewed by 1645

Abstract

In tribute to the bicentenary of the birth of Louis Pasteur, this report focuses on cyanotoxins, other natural products and bioactive compounds of cyanobacteria, a phylum of Gram-negative bacteria capable of carrying out oxygenic photosynthesis. These microbes have contributed to changes in the [...] Read more.

In tribute to the bicentenary of the birth of Louis Pasteur, this report focuses on cyanotoxins, other natural products and bioactive compounds of cyanobacteria, a phylum of Gram-negative bacteria capable of carrying out oxygenic photosynthesis. These microbes have contributed to changes in the geochemistry and the biology of Earth as we know it today. Furthermore, some bloom-forming cyanobacterial species are also well known for their capacity to produce cyanotoxins. This phylum is preserved in live cultures of pure, monoclonal strains in the Pasteur Cultures of Cyanobacteria (PCC) collection. The collection has been used to classify organisms within the Cyanobacteria of the bacterial kingdom and to investigate several characteristics of these bacteria, such as their ultrastructure, gas vacuoles and complementary chromatic adaptation. Thanks to the ease of obtaining genetic and further genomic sequences, the diversity of the PCC strains has made it possible to reveal some main cyanotoxins and to highlight several genetic loci dedicated to completely unknown natural products. It is the multidisciplinary collaboration of microbiologists, biochemists and chemists and the use of the pure strains of this collection that has allowed the study of several biosynthetic pathways from genetic origins to the structures of natural products and, eventually, their bioactivity. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

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11 pages, 623 KiB

Open AccessReview

From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone

by Daniela Ricci and Caroline Demangel

Toxins 2023, 15(6), 369; https://doi.org/10.3390/toxins15060369 - 30 May 2023

Cited by 1 | Viewed by 1461

Abstract

“Recognizing a surprising fact is the first step towards discovery.” This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study mycolactone, a lipid toxin produced by the human pathogen Mycobacterium ulcerans. M. ulcerans is the causative [...] Read more.

“Recognizing a surprising fact is the first step towards discovery.” This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study mycolactone, a lipid toxin produced by the human pathogen Mycobacterium ulcerans. M. ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease manifesting as chronic, necrotic skin lesions with a “surprising” lack of inflammation and pain. Decades after its first description, mycolactone has become much more than a mycobacterial toxin. This uniquely potent inhibitor of the mammalian translocon (Sec61) helped reveal the central importance of Sec61 activity for immune cell functions, the spread of viral particles and, unexpectedly, the viability of certain cancer cells. We report in this review the main discoveries that marked our research into mycolactone, and the medical perspectives they opened up. The story of mycolactone is not over and the applications of Sec61 inhibition may go well beyond immunomodulation, viral infections, and oncology. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

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16 pages, 361 KiB

Open AccessReview

Pasteurian Contributions to the Study of Bordetella pertussis Toxins

by Camille Locht

Toxins 2023, 15(3), 176; https://doi.org/10.3390/toxins15030176 - 25 Feb 2023

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Abstract

As a tribute to Louis Pasteur on the occasion of the 200th anniversary of his birth, this article summarizes the main contributions of scientists from Pasteur Institutes to the current knowledge of toxins produced by Bordetella pertussis. The article therefore focuses on [...] Read more.

As a tribute to Louis Pasteur on the occasion of the 200th anniversary of his birth, this article summarizes the main contributions of scientists from Pasteur Institutes to the current knowledge of toxins produced by Bordetella pertussis. The article therefore focuses on publications authored by researchers from Pasteur Institutes and is not intended as a systematic review of B. pertussis toxins. Besides identifying B. pertussis as the causative agent of whooping cough, Pasteurians have made several major contributions with respect to the structure–function relationship of the Bordetella lipo-oligosaccharide, adenylyl cyclase toxin and pertussis toxin. In addition to contributing to the understanding of these toxins’ mechanisms at the molecular and cellular levels and their role in pathogenesis, scientists at Pasteur Institutes have also exploited potential applications of the gathered knowledge of these toxins. These applications range from the development of novel tools to study protein–protein interactions over the design of novel antigen delivery tools, such as prophylactic or therapeutic vaccine candidates against cancer and viral infection, to the development of a live attenuated nasal pertussis vaccine. This scientific journey from basic science to applications in the field of human health matches perfectly with the overall scientific objectives outlined by Louis Pasteur himself. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

15 pages, 1867 KiB

Open AccessReview

Anaerobes and Toxins, a Tradition of the Institut Pasteur

by Michel R. Popoff and Sandra Legout

Toxins 2023, 15(1), 43; https://doi.org/10.3390/toxins15010043 - 05 Jan 2023

Cited by 2 | Viewed by 1906

Abstract

Louis Pasteur, one of the eminent pioneers of microbiology, discovered life without oxygen and identified the first anaerobic pathogenic bacterium. Certain bacteria were found to be responsible for specific diseases. Pasteur was mainly interested in the prevention and treatment of infectious diseases with [...] Read more.

Louis Pasteur, one of the eminent pioneers of microbiology, discovered life without oxygen and identified the first anaerobic pathogenic bacterium. Certain bacteria were found to be responsible for specific diseases. Pasteur was mainly interested in the prevention and treatment of infectious diseases with attenuated pathogens. The collaborators of Pasteur investigated the mechanisms of pathogenicity and showed that some bacterial soluble substances, called toxins, induce symptoms and lesions in experimental animals. Anaerobic bacteriology, which requires specific equipment, has emerged as a distinct part of microbiology. The first objectives were the identification and taxonomy of anaerobes. Several anaerobes producing potent toxins were associated with severe diseases. The investigation of toxins including sequencing, mode of action, and enzymatic activity led to a better understanding of toxin-mediated pathogenicity and allowed the development of safe and efficient prevention and treatment (vaccination with anatoxins, specific neutralizing antisera). Moreover, toxins turned out to be powerful tools in exploring cellular mechanisms supporting the concept of cellular microbiology. Pasteurians have made a wide contribution to anaerobic bacteriology and toxinology. The historical steps are summarized in this review. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

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13 pages, 2435 KiB

Open AccessReview

From Bacterial Poisons to Toxins: The Early Works of Pasteurians

by Jean-Marc Cavaillon

Toxins 2022, 14(11), 759; https://doi.org/10.3390/toxins14110759 - 03 Nov 2022

Cited by 6 | Viewed by 2569

Abstract

We review some of the precursor works of the Pasteurians in the field of bacterial toxins. The word “toxin” was coined in 1888 by Ludwig Brieger to qualify different types of poison released by bacteria. Pasteur had identified the bacteria as the cause [...] Read more.

We review some of the precursor works of the Pasteurians in the field of bacterial toxins. The word “toxin” was coined in 1888 by Ludwig Brieger to qualify different types of poison released by bacteria. Pasteur had identified the bacteria as the cause of putrefaction but never used the word toxin. In 1888, Émile Roux and Alexandre Yersin were the first to demonstrate that the bacteria causing diphtheria was releasing a deadly toxin. In 1923, Gaston Ramon treated that toxin with formalin and heat, resulting in the concept of “anatoxin” as a mean of vaccination. A similar approach was performed to obtain the tetanus anatoxin by Pierre Descombey, Christian Zoeller and G. Ramon. On his side, Elie Metchnikoff also studied the tetanus toxin and investigated the cholera toxin. His colleague from Odessa, Nikolaï GamaleÏa who was expected to join Institut Pasteur, wrote the first book on bacterial poisons while other Pasteurians such as Etienne Burnet, Maurice Nicolle, Emile Césari, and Constant Jouan wrote books on toxins. Concerning the endotoxins, Alexandre Besredka obtained the first immune antiserum against lipopolysaccharide, and André Boivin characterized the biochemical nature of the endotoxins in a work initiated with Lydia Mesrobeanu in Bucharest. Full article

(This article belongs to the Special Issue Pasteur, Toxins/Pathogenicity, Anti-toxins, a Bicentennial Contribution)

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