Special Issue "Toxins: The New Frontier for Understanding the Barrier between Commensalism and Pathogenicity?"

A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 11183

Special Issue Editor

Prof. Dr. Eric Oswald
E-Mail Website
Guest Editor
IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France, CHU Toulouse, Hôpital Purpan, Service de Bactériologie-Hygiène, Toulouse, France
Interests: bacterial toxins; genotoxicity; pathogenicity; enterobacteria
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Special Issue Information

Dear Colleagues,

By definition, toxins are toxic substances produced by a microorganism and responsible for its ability to cause disease. They have long been considered only as virulence factors having a deleterious effect on the host during acute infections. The fact that these toxins can be produced by nonpathogenic microorganisms and/or in asymptomatic carriers shows that we have often taken an overly simplistic approach to the role of these biologically very active molecules. Without paraphrasing Paracelsus who said that only the dose makes the poison, we must reconsider the role of these toxins not only during an acute infection, but also during the so-called asymptomatic carriage. At more “physiological” doses, toxins could have a totally different role and promote colonization by modulating the response of the host or the microbiota. However, like any drug, these substances have harmful side effects for the host, even without acute infections, in particular physiological contexts (inflammation, dysbiosis, etc.), during synergies with other xenobiotics or food contaminants, or simply because of the duration and recurrence of exposure (DNA damage, etc.). The production of these toxins can then play a role in the development of cancers, chronic inflammatory diseases, metabolic diseases, etc. Finally, we must also get away from a vision that focuses too much on the infection, which in fact represents a very short period of the life of a pathogenic microorganism. We too often forget that these microorganisms can have different hosts and reservoirs that play a crucial role in the infectious cycle. They can go through cycles in the environment where they fall prey to predators that may become future vectors for the spread of a pathogenic microorganism.

The aim of this Special Issue is therefore to review the role of these toxins from an angle that takes into account both the complexity of the infectious cycle of toxigenic microorganisms and the diversity of the effects of these toxins on the host, but also on the microbiota.

Prof. Dr. Eric Oswald
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Toxin
  • Commensalism
  • Pathogenicity
  • Infectious cycle
  • Microbiota
  • Metabolic diseases
  • Inflammation
  • Cancer

Published Papers (7 papers)

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Research

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Article
Helicobacter pylori CagA EPIYA Motif Variations Affect Metabolic Activity in B Cells
Toxins 2021, 13(9), 592; https://doi.org/10.3390/toxins13090592 - 24 Aug 2021
Viewed by 1344
Abstract
Background: Helicobacter pylori (Hp) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the Hp virulence factor cytotoxin-associated gene A (CagA) in pathogenesis. The pathogenic activity of CagA is [...] Read more.
Background: Helicobacter pylori (Hp) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the Hp virulence factor cytotoxin-associated gene A (CagA) in pathogenesis. The pathogenic activity of CagA is partly regulated by tyrosine phosphorylation of C-terminal Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in host cells. However, CagA differs considerably in EPIYA motifs, whose functions have been well characterized in epithelial cells. Since CagA is fragmented in immune cells, different CagA variants may exhibit undetected functions in B cells. Methods: B cells were infected with Hp isolates and isogenic mutants expressing different CagA EPIYA variants. CagA translocation and tyrosine phosphorylation were investigated by Western blotting. Apoptosis was analyzed by flow cytometry and metabolic activity was detected by an MTT assay. Results: Isogenic CagA EPIYA variants are equally well translocated into B cells, followed by tyrosine phosphorylation and cleavage. B cell apoptosis was induced in a CagA-independent manner. However, variants containing at least one EPIYA-C motif affected metabolic activity independently of phosphorylation or multiplication of EPIYA-C motifs. Conclusions: The diverse structure of CagA regulates B cell physiology, whereas B cell survival is independent of CagA. Full article
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Review

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Review
Cytolysin A (ClyA): A Bacterial Virulence Factor with Potential Applications in Nanopore Technology, Vaccine Development, and Tumor Therapy
Toxins 2022, 14(2), 78; https://doi.org/10.3390/toxins14020078 - 21 Jan 2022
Viewed by 1558
Abstract
Cytolysin A (ClyA) is a pore-forming toxin that is produced by some bacteria from the Enterobacteriaceae family. This review provides an overview of the current state of knowledge regarding ClyA, including the prevalence of the encoding gene and its transcriptional regulation, the secretion [...] Read more.
Cytolysin A (ClyA) is a pore-forming toxin that is produced by some bacteria from the Enterobacteriaceae family. This review provides an overview of the current state of knowledge regarding ClyA, including the prevalence of the encoding gene and its transcriptional regulation, the secretion pathway used by the protein, and the mechanism of protein assembly, and highlights potential applications of ClyA in biotechnology. ClyA expression is regulated at the transcriptional level, primarily in response to environmental stressors, and ClyA can exist stably both as a soluble monomer and as an oligomeric membrane complex. At high concentrations, ClyA induces cytolysis, whereas at low concentrations ClyA can affect intracellular signaling. ClyA is secreted in outer membrane vesicles (OMVs), which has important implications for biotechnology applications. For example, the native pore-forming ability of ClyA suggests that it could be used as a component of nanopore-based technologies, such as sequencing platforms. ClyA has also been exploited in vaccine development owing to its ability to present antigens on the OMV surface and provoke a robust immune response. In addition, ClyA alone or OMVs carrying ClyA fusion proteins have been investigated for their potential use as anti-tumor agents. Full article
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Review
The Cytotoxic Necrotizing Factors (CNFs)—A Family of Rho GTPase-Activating Bacterial Exotoxins
Toxins 2021, 13(12), 901; https://doi.org/10.3390/toxins13120901 - 15 Dec 2021
Viewed by 1062
Abstract
The cytotoxic necrotizing factors (CNFs) are a family of Rho GTPase-activating single-chain exotoxins that are produced by several Gram-negative pathogenic bacteria. Due to the pleiotropic activities of the targeted Rho GTPases, the CNFs trigger multiple signaling pathways and host cell processes with diverse [...] Read more.
The cytotoxic necrotizing factors (CNFs) are a family of Rho GTPase-activating single-chain exotoxins that are produced by several Gram-negative pathogenic bacteria. Due to the pleiotropic activities of the targeted Rho GTPases, the CNFs trigger multiple signaling pathways and host cell processes with diverse functional consequences. They influence cytokinesis, tissue integrity, cell barriers, and cell death, as well as the induction of inflammatory and immune cell responses. This has an enormous influence on host–pathogen interactions and the severity of the infection. The present review provides a comprehensive insight into our current knowledge of the modular structure, cell entry mechanisms, and the mode of action of this class of toxins, and describes their influence on the cell, tissue/organ, and systems levels. In addition to their toxic functions, possibilities for their use as drug delivery tool and for therapeutic applications against important illnesses, including nervous system diseases and cancer, have also been identified and are discussed. Full article
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Review
Tackling the Threat of Cancer Due to Pathobionts Producing Colibactin: Is Mesalamine the Magic Bullet?
Toxins 2021, 13(12), 897; https://doi.org/10.3390/toxins13120897 - 14 Dec 2021
Cited by 1 | Viewed by 1636
Abstract
Colibactin is a genotoxin produced primarily by Escherichia coli harboring the genomic pks island (pks+ E. coli). Pks+ E. coli cause host cell DNA damage, leading to chromosomal instability and gene mutations. The signature of colibactin-induced mutations [...] Read more.
Colibactin is a genotoxin produced primarily by Escherichia coli harboring the genomic pks island (pks+ E. coli). Pks+ E. coli cause host cell DNA damage, leading to chromosomal instability and gene mutations. The signature of colibactin-induced mutations has been described and found in human colorectal cancer (CRC) genomes. An inflamed intestinal environment drives the expansion of pks+ E. coli and promotes tumorigenesis. Mesalamine (i.e., 5-aminosalycilic acid), an effective anti-inflammatory drug, is an inhibitor of the bacterial polyphosphate kinase (PPK). This drug not only inhibits the production of intestinal inflammatory mediators and the proliferation of CRC cells, but also limits the abundance of E. coli in the gut microbiota and diminishes the production of colibactin. Here, we describe the link between intestinal inflammation and colorectal cancer induced by pks+ E. coli. We discuss the potential mechanisms of the pleiotropic role of mesalamine in treating both inflammatory bowel diseases and reducing the risk of CRC due to pks+ E. coli. Full article
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Review
Amoebae as Targets for Toxins or Effectors Secreted by Mammalian Pathogens
Toxins 2021, 13(8), 526; https://doi.org/10.3390/toxins13080526 - 28 Jul 2021
Viewed by 1081
Abstract
Numerous microorganisms, pathogenic for mammals, come from the environment where they encounter predators such as free-living amoebae (FLA). The selective pressure due to this interaction could have generated virulence traits that are deleterious for amoebae and represents a weapon against mammals. Toxins are [...] Read more.
Numerous microorganisms, pathogenic for mammals, come from the environment where they encounter predators such as free-living amoebae (FLA). The selective pressure due to this interaction could have generated virulence traits that are deleterious for amoebae and represents a weapon against mammals. Toxins are one of these powerful tools that are essential for bacteria or fungi to survive. Which amoebae are used as a model to study the effects of toxins? What amoeba functions have been reported to be disrupted by toxins and bacterial secreted factors? Do bacteria and fungi effectors affect eukaryotic cells similarly? Here, we review some studies allowing to answer these questions, highlighting the necessity to extend investigations of microbial pathogenicity, from mammals to the environmental reservoir that are amoebae. Full article
Review
Bacterial Toxins Are a Never-Ending Source of Surprises: From Natural Born Killers to Negotiators
Toxins 2021, 13(6), 426; https://doi.org/10.3390/toxins13060426 - 17 Jun 2021
Cited by 2 | Viewed by 1674
Abstract
The idea that bacterial toxins are not only killers but also execute more sophisticated roles during bacteria–host interactions by acting as negotiators has been highlighted in the past decades. Depending on the toxin, its cellular target and mode of action, the final regulatory [...] Read more.
The idea that bacterial toxins are not only killers but also execute more sophisticated roles during bacteria–host interactions by acting as negotiators has been highlighted in the past decades. Depending on the toxin, its cellular target and mode of action, the final regulatory outcome can be different. In this review, we have focused on two families of bacterial toxins: genotoxins and pore-forming toxins, which have different modes of action but share the ability to modulate the host’s immune responses, independently of their capacity to directly kill immune cells. We have addressed their immuno-suppressive effects with the perspective that these may help bacteria to avoid clearance by the host’s immune response and, concomitantly, limit detrimental immunopathology. These are optimal conditions for the establishment of a persistent infection, eventually promoting asymptomatic carriers. This immunomodulatory effect can be achieved with different strategies such as suppression of pro-inflammatory cytokines, re-polarization of the immune response from a pro-inflammatory to a tolerogenic state, and bacterial fitness modulation to favour tissue colonization while preventing bacteraemia. An imbalance in each of those effects can lead to disease due to either uncontrolled bacterial proliferation/invasion, immunopathology, or both. Full article
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Review
Escherichia coli Shiga Toxins and Gut Microbiota Interactions
Toxins 2021, 13(6), 416; https://doi.org/10.3390/toxins13060416 - 11 Jun 2021
Cited by 8 | Viewed by 2085
Abstract
Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are enterohemorrhagic bacteria that induce hemorrhagic colitis. This, in turn, may result in potentially lethal complications, such as hemolytic uremic syndrome (HUS), which is characterized by thrombocytopenia, acute renal failure, and neurological abnormalities. Both species [...] Read more.
Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are enterohemorrhagic bacteria that induce hemorrhagic colitis. This, in turn, may result in potentially lethal complications, such as hemolytic uremic syndrome (HUS), which is characterized by thrombocytopenia, acute renal failure, and neurological abnormalities. Both species of bacteria produce Shiga toxins (Stxs), a phage-encoded exotoxin inhibiting protein synthesis in host cells that are primarily responsible for bacterial virulence. Although most studies have focused on the pathogenic roles of Stxs as harmful substances capable of inducing cell death and as proinflammatory factors that sensitize the host target organs to damage, less is known about the interface between the commensalism of bacterial communities and the pathogenicity of the toxins. The gut contains more species of bacteria than any other organ, providing pathogenic bacteria that colonize the gut with a greater number of opportunities to encounter other bacterial species. Notably, the presence in the intestines of pathogenic EHEC producing Stxs associated with severe illness may have compounding effects on the diversity of the indigenous bacteria and bacterial communities in the gut. The present review focuses on studies describing the roles of Stxs in the complex interactions between pathogenic Shiga toxin-producing E. coli, the resident microbiome, and host tissues. The determination of these interactions may provide insights into the unresolved issues regarding these pathogens. Full article
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