Bacterial Toxins – the Key Causal and Preventive Markers of Bacterial Disease

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 11833

Special Issue Editor


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Guest Editor
University of Cambridge, Cambridge, United Kingdom
Interests: Vaccines, Diagnostics, Evolution, Epidemiology, Public Health, Global Health

Special Issue Information

Bacterial toxins are the one of the most crucial and potent tools that bacteria deploy in mechanistic infection and disease pathology. These key virulence markers can be involved in a variety of functions ranging from colonisation (by damaging cells and tissues), to enhanced pathogenesis (by disabling the innate and adaptive defences of host.) In special cases, these entities also help in faster transmission and spread of bacteria and disease.

Broadly, toxins can be classed into two types: exotoxin (acellular) and endotoxin (cellular). Exotoxins such as neurotoxins of Clostridium botulinum and Clostridium tetani, anthrax toxin of Bacillus anthracis, diarrheal toxin of Vibrio cholerae and ETEC, immunostimulatory superantigens (SAgs) of Staphylococcus aureus and Streptococcus pyogenes and choking toxins of Corynebacterium diphtheriae and Bordetella pertussis among many others, all modulate host cell function pathways. Endotoxins on the contrary are the lipopolysaccharides of bacterial cells and generally work as pyrogens. Due to their critical role in infection and disease, bacterial toxins make most convenient vaccine and therapeutic targets. Also, due to their immunomodulatory properties, modified versions of bacterial toxins are widely used as carrier proteins and adjuvants. 

This Special Issue of Toxins will detail the history, evolution, and the mechanisms of action and host interaction of various bacterial toxins. In this issue, we will also showcase how these bacterial toxins have been exploited in advancement of scientific research, diagnostics, biochemistry-based high-throughput technologies and as components of life-saving drugs and vaccine formulations.

Dr. Ankur Mutreja
Guest Editor

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Keywords

  • Exotoxin
  • endotoxin
  • superantigen
  • toxoid
  • anti-toxin
  • bacteria
  • vaccine
  • engineering
  • carrier protein
  • adjuvant

Published Papers (3 papers)

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Research

14 pages, 2809 KiB  
Article
Association of Polygenic Risk Score and Bacterial Toxins at Screening Colonoscopy with Colorectal Cancer Progression: A Multicenter Case-Control Study
by Alfonso Piciocchi, Elena Angela Pia Germinario, Koldo Garcia Etxebarria, Silvia Rossi, Lupe Sanchez-Mete, Barbara Porowska, Vittoria Stigliano, Paolo Trentino, Andrea Oddi, Fabio Accarpio, Gian Luca Grazi, Giovanni Bruno, Massimo Bonucci, Massimo Giambenedetti, Patrizia Spigaglia, Fabrizio Barbanti, Slawomir Owczarek, Ida Luzzi, Elisabetta Delibato, Zaira Maroccia, Lorenza Nisticò, Carla Fiorentini, Mauro D’Amato, Roberta De Angelis and Alessia Fabbriadd Show full author list remove Hide full author list
Toxins 2021, 13(8), 569; https://doi.org/10.3390/toxins13080569 - 16 Aug 2021
Cited by 13 | Viewed by 4725
Abstract
Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and its incidence is correlated with infections, chronic inflammation, diet, and genetic factors. An emerging aspect is that microbial dysbiosis and chronic infections triggered by certain bacteria can be risk factors for [...] Read more.
Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and its incidence is correlated with infections, chronic inflammation, diet, and genetic factors. An emerging aspect is that microbial dysbiosis and chronic infections triggered by certain bacteria can be risk factors for tumor progression. Recent data suggest that certain bacterial toxins implicated in DNA attack or in proliferation, replication, and death can be risk factors for insurgence and progression of CRC. In this study, we recruited more than 300 biopsy specimens from people undergoing colonoscopy, and we analyzed to determine whether a correlation exists between the presence of bacterial genes coding for toxins possibly involved in CRC onset and progression and the different stages of CRC. We also analyzed to determine whether CRC-predisposing genetic factors could contribute to bacterial toxins response. Our results showed that CIF toxin is associated with polyps or adenomas, whereas pks+ seems to be a predisposing factor for CRC. Toxins from Escherichia coli as a whole have a higher incidence rate in adenocarcinoma patients compared to controls, whereas Bacteroides fragilis toxin does not seem to be associated with pre-cancerous nor with cancerous lesions. These results have been obtained irrespectively of the presence of CRC-risk loci. Full article
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11 pages, 551 KiB  
Article
Molecular Characterization of the Enterohemolysin Gene (ehxA) in Clinical Shiga Toxin-Producing Escherichia coli Isolates
by Ying Hua, Ji Zhang, Cecilia Jernberg, Milan Chromek, Sverker Hansson, Anne Frykman, Yanwen Xiong, Chengsong Wan, Andreas Matussek and Xiangning Bai
Toxins 2021, 13(1), 71; https://doi.org/10.3390/toxins13010071 - 19 Jan 2021
Cited by 10 | Viewed by 3028
Abstract
Shiga toxin (Stx)-producing Escherichia coli (STEC) is an important foodborne pathogen with the ability to cause bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Little is known about enterohemolysin-encoded by ehxA. Here we investigated the prevalence and diversity of ehxA in 239 [...] Read more.
Shiga toxin (Stx)-producing Escherichia coli (STEC) is an important foodborne pathogen with the ability to cause bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Little is known about enterohemolysin-encoded by ehxA. Here we investigated the prevalence and diversity of ehxA in 239 STEC isolates from human clinical samples. In total, 199 out of 239 isolates (83.26%) were ehxA positive, and ehxA was significantly overrepresented in isolates carrying stx2a + stx2c (p < 0.001) and eae (p < 0.001). The presence of ehxA was significantly associated with BD and serotype O157:H7. Five ehxA subtypes were identified, among which, ehxA subtypes B, C, and F were overrepresented in eae-positive isolates. All O157:H7 isolates carried ehxA subtype B, which was related to BD and HUS. Three ehxA groups were observed in the phylogenetic analysis, namely, group Ⅰ (ehxA subtype A), group Ⅱ (ehxA subtype B, C, and F), and group Ⅲ (ehxA subtype D). Most BD- and HUS-associated isolates were clustered into ehxA group Ⅱ, while ehxA group Ⅰ was associated with non-bloody stool and individuals ≥10 years of age. The presence of ehxA + eae and ehxA + eae + stx2 was significantly associated with HUS and O157:H7 isolates. In summary, this study showed a high prevalence and the considerable genetic diversity of ehxA among clinical STEC isolates. The ehxA genotypes (subtype B and phylogenetic group Ⅱ) could be used as risk predictors, as they were associated with severe clinical symptoms, such as BD and HUS. Furthermore, ehxA, together with stx and eae, can be used as a risk predictor for HUS in STEC infections. Full article
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14 pages, 1406 KiB  
Article
High Titer Persistent Neutralizing Antibodies Induced by TSST-1 Variant Vaccine Against Toxic Shock Cytokine Storm
by Andreas Roetzer, Norbert Stich, Nina Model, Michael Schwameis, Christa Firbas, Bernd Jilma and Martha M. Eibl
Toxins 2020, 12(10), 640; https://doi.org/10.3390/toxins12100640 - 02 Oct 2020
Cited by 6 | Viewed by 2503
Abstract
Staphylococcal superantigen toxins lead to a devastating cytokine storm resulting in shock and multi-organ failure. We have previously assessed the safety and immunogenicity of a recombinant toxic shock syndrome toxin 1 variant vaccine (rTSST-1v) in clinical trials (NCT02971670 and NCT02340338). The current study [...] Read more.
Staphylococcal superantigen toxins lead to a devastating cytokine storm resulting in shock and multi-organ failure. We have previously assessed the safety and immunogenicity of a recombinant toxic shock syndrome toxin 1 variant vaccine (rTSST-1v) in clinical trials (NCT02971670 and NCT02340338). The current study assessed neutralizing antibody titers after repeated vaccination with escalating doses of rTSST-1v. At study entry, 23 out of 34 subjects (67.6%) had neutralizing antibody titers inhibiting T cell activation as determined by 3H-thymidine incorporation at a serum dilution of ≤1:100 with similar figures for inhibition of IL-2 activation (19 of 34 subjects, 55.9%) as assessed by quantitative PCR. After the first vaccination, numbers of subjects with neutralization titers inhibiting T cell activation (61.7% ≥ 1:1000) and inhibiting IL-2 gene induction (88.2% ≥ 1:1000) increased. The immune response was augmented after the second vaccination (inhibiting T cell activation: 78.8% ≥ 1:1000; inhibiting IL-2 induction: 93.9% ≥ 1:1000) corroborated with a third immunization months later in a small subgroup of subjects. Assessment of IFNγ, TNFα and IL-6 inhibition revealed similar results, whereas neutralization titers did not change in placebo participants. Antibody titer studies show that vaccination with rTSST-1v in subjects with no/low neutralizing antibodies can rapidly induce high titer neutralizing antibodies persisting over months. Full article
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