Special Issue "Immunotherapies and Vaccines against Diseases Caused by Staphylococcal Toxins"

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

Deadline for manuscript submissions: closed (31 May 2020).

Special Issue Editor

Dr. M. Javad Aman
Website
Guest Editor
Integrated Biotherapeutics Inc., Rockville, MD 20850, USA
Interests: Staphylococcus aureus; toxoid vaccine; monoclonal antibodies; immune response; vaccine development

Special Issue Information

Dear Colleagues,

Staphylococcus aureus (SA) is a human commensal and, at the same time, formidable pathogen that can cause a wide range of diseases, from skin and soft tissue infections to life threatening bacteremia, pneumonia, surgical site infections, and osteomyelitis. The growing prevalence of methicillin-resistant SA (MRSA), as well as multidrug resistant strains, represents a major public health challenge. SA has a large arsenal of virulence factors that help establish the infection and to evade host immune defenses.  Several of these factors, notably, all cell-associated, were evaluated as vaccine and immunotherapy targets in human efficacy trials, but they all either lacked efficacy or resulted in more severe disease. S. aureus also produces many secreted toxins that modulate host immune responses, kill key innate immune cells, intoxicate components of the adaptive immune response, cause barrier dysfunction enabling bacterial dissemination, help extract nutrients from the host, cause excessive inflammation, promote platelet aggregation, and induce toxic shock. These toxins include pore-forming toxins (PFTs), including alpha hemolysin and bicomponent PFTs; more than twenty superantigens (SAgs); SAg-like toxins (SSLs); delta toxin; phenol soluble modulins (PSMs); and exfoliative toxins. Recent data in several animal models indicate that neutralizing key toxins can facilitate immune-mediated SA clearance. Epidemiologically, some of these toxins, such as Panton-Valentine leukocidin (PVL) and PSM, have been linked to the emergence of community acquired MRSA (CA-MRSA) in the past two decades. Alpha hemolysin and PVL have emerged as critical virulence factors for necrotizing pneumonia and skin and soft tissue infections. Superantigens are the main cause of staphylococcal toxic shock syndrome (TSST) and food poisoning, and are also implicated in atopic dermatitis and other forms of allergic diseases.

Thus, staphylococcal toxins should be considered important targets of vaccine and immunotherapy. While animal studies and epidemiological evidence support this notion, many questions and challenges remain to be addressed.  Which one of the numerous toxins produced by S. aureus must be targeted, and for which staphylococcal syndromes? Can the neutralization of toxins prevent infection? Can severity endpoints be defined that allow for measurable clinical outcomes? Can anti-toxin strategies be used to mitigate flares of atopic disease?

The focus of this Special Issue of Toxins is on staphylococcal toxins as the target of vaccines and immunotherapy. This will include a wide range of topics, such as a deeper understanding of the interaction of the toxins with the host; immune modulation by the toxins and its role in pathogenesis; epidemiological and clinical evidence for the role of toxins in SA diseases; and animal models and studies evaluating toxoid vaccine or anti-toxin immunotherapeutic candidates.

Dr. M. Javad Aman
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 papers will be 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 2000 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

  • Staphylococcus aureus
  • staphylococcal toxins
  • pore-forming toxins
  • superantigens
  • immunotherapy
  • toxoid vaccine
  • immune evasion
  • anti-virulence vaccine

Published Papers (2 papers)

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Review

Open AccessReview
Allergy—A New Role for T Cell Superantigens of Staphylococcus aureus?
Toxins 2020, 12(3), 176; https://doi.org/10.3390/toxins12030176 - 12 Mar 2020
Abstract
Staphylococcus aureus superantigens (SAgs) are among the most potent T cell mitogens known. They stimulate large fractions of T cells by cross-linking their T cell receptor with major histocompatibility complex class-II molecules on antigen presenting cells, resulting in T cell proliferation and massive [...] Read more.
Staphylococcus aureus superantigens (SAgs) are among the most potent T cell mitogens known. They stimulate large fractions of T cells by cross-linking their T cell receptor with major histocompatibility complex class-II molecules on antigen presenting cells, resulting in T cell proliferation and massive cytokine release. To date, 26 different SAgs have been described in the species S. aureus; they comprise the toxic shock syndrome toxin (TSST-1), as well as 25 staphylococcal enterotoxins (SEs) or enterotoxin-like proteins (SEls). SAgs can cause staphylococcal food poisoning and toxic shock syndrome and contribute to the clinical symptoms of staphylococcal infection. In addition, there is growing evidence that SAgs are involved in allergic diseases. This review provides an overview on recent epidemiological data on the involvement of S. aureus SAgs and anti-SAg-IgE in allergy, demonstrating that being sensitized to SEs—in contrast to inhalant allergens—is associated with a severe disease course in patients with chronic airway inflammation. The mechanisms by which SAgs trigger or amplify allergic immune responses, however, are not yet fully understood. Here, we discuss known and hypothetical pathways by which SAgs can drive an atopic disease. Full article
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Open AccessReview
The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections
Toxins 2019, 11(6), 332; https://doi.org/10.3390/toxins11060332 - 11 Jun 2019
Abstract
Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both [...] Read more.
Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies. Full article
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