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Toxins
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Pertussis Toxin
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Pertussis Toxin

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

Deadline for manuscript submissions: closed (31 May 2019) | Viewed by 33123

Special Issue Editor

Prof. Nicholas H. Carbonetti

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Guest Editor
Department of Microbiology & Immunology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA

Special Issue Information

Dear Colleagues,

Pertussis toxin (PT) is a major virulence factor of Bordetella pertussis, the bacterial pathogen responsible for the disease pertussis (whooping cough). PT is a multisubunit protein toxin that enters mammalian cells, ADP-ribosylates Gi proteins, and thereby inhibits G protein-coupled receptor signaling through this class of G proteins. Because of this activity, PT has been widely used as a tool in cell biology and signaling studies. More importantly, PT is a central player in the biology of B. pertussis, the pathogenesis of pertussis disease, the diagnosis of pertussis infections, and the prevention of pertussis by vaccination. Each of these aspects will be covered in this Special Issue focusing on the many and varied features of PT.

Prof. Nicholas H. Carbonetti
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 2700 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

  • Pertussis
  • Bordetella
  • ADP-ribosylation
  • G protein
  • G protein-coupled receptor signaling
  • pathogenesis
  • vaccine
  • diagnosis
  • leukocytosis

Published Papers (4 papers)

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Review

12 pages, 248 KiB  
Review
Pertussis Toxin: A Key Component in Pertussis Vaccines?
by Kelsey A. Gregg and Tod J. Merkel
Toxins 2019, 11(10), 557; https://doi.org/10.3390/toxins11100557 - 21 Sep 2019
Cited by 14 | Viewed by 5641
Abstract
B. pertussis is a human-specific pathogen and the causative agent of whooping cough. The ongoing resurgence in pertussis incidence in high income countries is likely due to faster waning of immunity and increased asymptomatic colonization in individuals vaccinated with acellular pertussis (aP) vaccine [...] Read more.
B. pertussis is a human-specific pathogen and the causative agent of whooping cough. The ongoing resurgence in pertussis incidence in high income countries is likely due to faster waning of immunity and increased asymptomatic colonization in individuals vaccinated with acellular pertussis (aP) vaccine relative whole-cell pertussis (wP)-vaccinated individuals. This has renewed interest in developing more effective vaccines and treatments and, in support of these efforts, defining pertussis vaccine correlates of protection and the role of vaccine antigens and toxins in disease. Pertussis and its toxins have been investigated by scientists for over a century, yet we still do not have a clear understanding of how pertussis toxin (PT) contributes to disease symptomology or how anti-PT immune responses confer protection. This review covers PT’s role in disease and evidence for its protective role in vaccines. Clinical data suggest that PT is a defining and essential toxin for B. pertussis pathogenesis and, when formulated into a vaccine, can prevent disease. Additional studies are required to further elucidate the role of PT in disease and vaccine-mediated protection, to inform the development of more effective treatments and vaccines. Full article
(This article belongs to the Special Issue Pertussis Toxin)
12 pages, 1097 KiB  
Review
Intracellular Trafficking and Translocation of Pertussis Toxin
by Ken Teter
Toxins 2019, 11(8), 437; https://doi.org/10.3390/toxins11080437 - 25 Jul 2019
Cited by 14 | Viewed by 4018
Abstract
Pertussis toxin (PT) is a multimeric complex of six proteins. The PTS1 subunit is an ADP-ribosyltransferase that inactivates the alpha subunit of heterotrimeric Gi/o proteins. The remaining PT subunits form a pentamer that positions PTS1 in and above the central [...] Read more.
Pertussis toxin (PT) is a multimeric complex of six proteins. The PTS1 subunit is an ADP-ribosyltransferase that inactivates the alpha subunit of heterotrimeric Gi/o proteins. The remaining PT subunits form a pentamer that positions PTS1 in and above the central cavity of the triangular structure. Adhesion of this pentamer to glycoprotein or glycolipid conjugates on the surface of a target cell leads to endocytosis of the PT holotoxin. Vesicle carriers then deliver the holotoxin to the endoplasmic reticulum (ER) where PTS1 dissociates from the rest of the toxin, unfolds, and exploits the ER-associated degradation pathway for export to the cytosol. Refolding of the cytosolic toxin allows it to regain an active conformation for the disruption of cAMP-dependent signaling events. This review will consider the intracellular trafficking of PT and the order-disorder-order transitions of PTS1 that are essential for its cellular activity. Full article
(This article belongs to the Special Issue Pertussis Toxin)
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19 pages, 298 KiB  
Review
Assays for Determining Pertussis Toxin Activity in Acellular Pertussis Vaccines
by Kevin Markey, Catpagavalli Asokanathan and Ian Feavers
Toxins 2019, 11(7), 417; https://doi.org/10.3390/toxins11070417 - 17 Jul 2019
Cited by 14 | Viewed by 3625
Abstract
Whooping cough is caused by the bacterium Bordetella pertussis. There are currently two types of vaccines that can prevent the disease; whole cell vaccines (WCV) and acellular vaccines (ACV). The main virulence factor produced by the organism is pertussis toxin (PTx). This [...] Read more.
Whooping cough is caused by the bacterium Bordetella pertussis. There are currently two types of vaccines that can prevent the disease; whole cell vaccines (WCV) and acellular vaccines (ACV). The main virulence factor produced by the organism is pertussis toxin (PTx). This toxin is responsible for many physiological effects on the host, but it is also immunogenic and in its detoxified form is the main component of all ACVs. In producing toxoid for vaccines, it is vital to achieve a balance between sufficiently detoxifying PTx to render it safe while maintaining enough molecular structure that it retains its protective immunogenicity. To ensure that the first part of this balancing act has been successfully achieved, assays are required to accurately measure residual PTx activity in ACV products accurately. Quality control assays are also required to ensure that the detoxification procedures are robust and stable. This manuscript reviews the methods that have been used to achieve this aim, or may have the potential to replace them, and highlights their continuing requirement as vaccines that induce a longer lasting immunity are developed to prevent the re-occurrence of outbreaks that have been observed recently. Full article
(This article belongs to the Special Issue Pertussis Toxin)
14 pages, 604 KiB  
Review
Association of Pertussis Toxin with Severe Pertussis Disease
by Karen Scanlon, Ciaran Skerry and Nicholas Carbonetti
Toxins 2019, 11(7), 373; https://doi.org/10.3390/toxins11070373 - 27 Jun 2019
Cited by 38 | Viewed by 18873
Abstract
Pertussis, caused by respiratory tract infection with the bacterial pathogen Bordetella pertussis, has long been considered to be a toxin-mediated disease. Bacteria adhere and multiply extracellularly in the airways and release several toxins, which have a variety of effects on the host, [...] Read more.
Pertussis, caused by respiratory tract infection with the bacterial pathogen Bordetella pertussis, has long been considered to be a toxin-mediated disease. Bacteria adhere and multiply extracellularly in the airways and release several toxins, which have a variety of effects on the host, both local and systemic. Predominant among these toxins is pertussis toxin (PT), a multi-subunit protein toxin that inhibits signaling through a subset of G protein-coupled receptors in mammalian cells. PT activity has been linked with severe and lethal pertussis disease in young infants and a detoxified version of PT is a common component of all licensed acellular pertussis vaccines. The role of PT in typical pertussis disease in other individuals is less clear, but significant evidence supporting its contribution to pathogenesis has been accumulated from animal model studies. In this review we discuss the evidence indicating a role for PT in pertussis disease, focusing on its contribution to severe pertussis in infants, modulation of immune and inflammatory responses to infection, and the characteristic paroxysmal cough of pertussis. Full article
(This article belongs to the Special Issue Pertussis Toxin)
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