-
Clinical Microbiology Reviews Jun 2020In the 1980s, menstrual toxic shock syndrome (mTSS) became a household topic, particularly among mothers and their daughters. The research performed at the time, and for... (Review)
Review
In the 1980s, menstrual toxic shock syndrome (mTSS) became a household topic, particularly among mothers and their daughters. The research performed at the time, and for the first time, exposed the American public as well as the biomedical community, in a major way, to understanding disease progression and investigation. Those studies led to the identification of the cause, and the pyrogenic toxin superantigen TSS toxin 1 (TSST-1), and many of the risk factors, for example, tampon use. Those studies in turn led to TSS warning labels on the outside and inside of tampon boxes and, as important, uniform standards worldwide of tampon absorbency labeling. This review addresses our understanding of the development and conclusions related to mTSS and risk factors. We leave the final message that even though mTSS is not commonly in the news today, cases continue to occur. Additionally, strains cycle in human populations in roughly 10-year intervals, possibly dependent on immune status. TSST-1-producing bacteria appear to be reemerging, suggesting that physician awareness of this emergence and mTSS history should be heightened.
Topics: Bacterial Toxins; Enterotoxins; Female; Humans; Menstrual Hygiene Products; Menstruation; Risk Factors; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus; Superantigens
PubMed: 32461307
DOI: 10.1128/CMR.00032-19 -
PLoS Pathogens Dec 2021Streptococcus pyogenes (group A Streptococcus) is a globally disseminated and human-adapted bacterial pathogen that causes a wide range of infections, including scarlet... (Review)
Review
Streptococcus pyogenes (group A Streptococcus) is a globally disseminated and human-adapted bacterial pathogen that causes a wide range of infections, including scarlet fever. Scarlet fever is a toxin-mediated disease characterized by the formation of an erythematous, sandpaper-like rash that typically occurs in children aged 5 to 15. This infectious disease is caused by toxins called superantigens, a family of highly potent immunomodulators. Although scarlet fever had largely declined in both prevalence and severity since the late 19th century, outbreaks have now reemerged in multiple geographical regions over the past decade. Here, we review recent findings that address the role of superantigens in promoting a fitness advantage for S. pyogenes within human populations and discuss how superantigens may be suitable targets for vaccination strategies.
Topics: Adolescent; Antigens, Bacterial; Child; Child, Preschool; Female; Humans; Male; Scarlet Fever; Streptococcus pyogenes; Superantigens
PubMed: 34969060
DOI: 10.1371/journal.ppat.1010097 -
Clinical Microbiology and Infection :... Jul 2023Epidemiological and whole-genome sequencing analysis of an ongoing outbreak of Streptococcus pyogenes (Group A Streptococcus) in London (United Kingdom).
OBJECTIVES
Epidemiological and whole-genome sequencing analysis of an ongoing outbreak of Streptococcus pyogenes (Group A Streptococcus) in London (United Kingdom).
METHODS
Prospective identification of Group A Streptococcus cases from a diagnostic laboratory serving central and south London between 27 November and 10 December 2022. Case notes were reviewed and isolates were retrieved. Case numbers were compared with the previous 5 years. Whole-genome sequencing was performed with long-read, nanopore technology for emm typing and identification of superantigen genes. Associations of pathogen-related factors with an invasive disease were assessed by single-variable and multi-variable logistic regression.
RESULTS
Case numbers began increasing in October 2022 from a baseline of 2.0 cases per day, and in December 2022, the average daily case numbers reached 10.8 cases per day, four-fold the number usually seen in winter. A total of 113 cases were identified during the prospective study period. Three quarters (86/113, 76%) were paediatric cases, including 2 deaths. Of 113 cases, 11 (10%) were invasive. In total, 56 isolates were successfully sequenced, including 10 of 11 (91%) invasive isolates. The emm12 (33/56, 59%) and emm1 (9/56, 16%) types were predominant, with 7 of 9 (78%) emm1 isolates being from the M1uk clone. The majority of invasive isolates had superantigen genes spea (7/10, 70%) and spej (8/10, 80%), whereas, in non-invasive isolates, these superantigen genes were found less frequently (spea: 5/46, 11% and spej: 7/46, 15%). By multivariable analysis of pathogen-related factors, spea (OR 8.9, CI 1.4-57, p 0.020) and spej (OR 12, CI 1.8-78, p 0.011) were associated with invasive disease.
CONCLUSIONS
emm12 and emm1 types predominate in the ongoing outbreak, which mainly affects children. In this outbreak, the spea and spej superantigen genes are associated with the severity of presentation.
Topics: Child; Humans; Streptococcus pyogenes; Prospective Studies; Molecular Epidemiology; London; Antigens, Bacterial; United Kingdom; Superantigens; Disease Outbreaks; Streptococcal Infections; Bacterial Outer Membrane Proteins
PubMed: 36925107
DOI: 10.1016/j.cmi.2023.03.001 -
Frontiers in Immunology 2021Superantigens are unconventional antigens which recognise immune receptors outside their usual recognition sites e.g. complementary determining regions (CDRs), to elicit... (Review)
Review
Superantigens are unconventional antigens which recognise immune receptors outside their usual recognition sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulins on B-cells, affecting opsonisation, IgG-mediated phagocytosis, and driving apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.
Topics: Animals; Antibodies; Antigen-Presenting Cells; Apoptosis; B-Lymphocytes; Clonal Anergy; Cytokine Release Syndrome; Histocompatibility Antigens Class II; Humans; Immunoglobulin Fragments; Lymphocyte Activation; Protein Engineering; Receptors, Antigen, T-Cell; Signal Transduction; Superantigens; T-Lymphocytes
PubMed: 34616400
DOI: 10.3389/fimmu.2021.731845 -
Clinical Microbiology Reviews Jul 2013SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens... (Review)
Review
SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies.
Topics: Animals; Exotoxins; Humans; Models, Molecular; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes; Superantigens
PubMed: 23824366
DOI: 10.1128/CMR.00104-12 -
European Review For Medical and... Feb 2021Bacterial superantigens (SAgs) are proteins produced by few types of bacteria that have been linked to several human diseases. Due to their potent in vitro and in vivo... (Review)
Review
Bacterial superantigens (SAgs) are proteins produced by few types of bacteria that have been linked to several human diseases. Due to their potent in vitro and in vivo tumoricidal effects, they are extensively investigated for oncological applications either alone or in combination with classical anticancer drugs. However, the intrinsic toxicity of natural SAgs stimulated the development of more effective and less toxic SAg-based immunotherapy. This review summarizes our current knowledge on SAg-based immunotherapy including SAg-like proteins and SAg derivatives, as well as their potential alone or with other therapeutic modalities including chemotherapy and radiotherapy.
Topics: Animals; Antigens, Bacterial; Humans; Immunotherapy; Neoplasms; Superantigens
PubMed: 33629332
DOI: 10.26355/eurrev_202102_24873 -
Toxins Nov 2018During severe bacterial infections, death and disease are often caused by an overly strong immune response of the human host. Acute toxic shock is induced by... (Review)
Review
During severe bacterial infections, death and disease are often caused by an overly strong immune response of the human host. Acute toxic shock is induced by superantigen toxins, a diverse set of proteins secreted by Gram-positive staphylococcal and streptococcal bacterial strains that overstimulate the inflammatory response by orders of magnitude. The need to protect from superantigen toxins led to our discovery that in addition to the well-known MHC class II and T cell receptors, the principal costimulatory receptor, CD28, and its constitutively expressed coligand, B7-2 (CD86), previously thought to have only costimulatory function, are actually critical superantigen receptors. Binding of the superantigen into the homodimer interfaces of these costimulatory receptors greatly enhances B7-2/CD28 engagement, leading to excessive pro-inflammatory signaling. This finding led to the design of short receptor dimer interface mimetic peptides that block the binding of superantigen and thus protect from death. It then turned out that such a peptide will protect also from Gram-negative bacterial infection and from polymicrobial sepsis. One such CD28 mimetic peptide is advancing in a Phase 3 clinical trial to protect from lethal wound infections by flesh-eating bacteria. These host-oriented therapeutics target the human immune system itself, rendering pathogens less likely to become resistant.
Topics: Animals; Bacterial Toxins; CD28 Antigens; Drug Development; Humans; Superantigens
PubMed: 30404186
DOI: 10.3390/toxins10110459 -
Toxins Aug 2010Staphylococcus aureus (S. aureus) is a Gram positive bacterium that is carried by about one third of the general population and is responsible for common and serious... (Review)
Review
Staphylococcus aureus (S. aureus) is a Gram positive bacterium that is carried by about one third of the general population and is responsible for common and serious diseases. These diseases include food poisoning and toxic shock syndrome, which are caused by exotoxins produced by S. aureus. Of the more than 20 Staphylococcal enterotoxins, SEA and SEB are the best characterized and are also regarded as superantigens because of their ability to bind to class II MHC molecules on antigen presenting cells and stimulate large populations of T cells that share variable regions on the β chain of the T cell receptor. The result of this massive T cell activation is a cytokine bolus leading to an acute toxic shock. These proteins are highly resistant to denaturation, which allows them to remain intact in contaminated food and trigger disease outbreaks. A recognized problem is the emergence of multi-drug resistant strains of S. aureus and these are a concern in the clinical setting as they are a common cause of antibiotic-associated diarrhea in hospitalized patients. In this review, we provide an overview of the current understanding of these proteins.
Topics: Animals; Biological Warfare Agents; Diarrhea; Enterotoxins; Humans; Staphylococcal Food Poisoning; Staphylococcus aureus; Superantigens
PubMed: 22069679
DOI: 10.3390/toxins2082177 -
The Journal of Investigative Dermatology Apr 2022A potential role of Staphylococcus aureus in bullous pemphigoid was explored by examining the colonization rate in patients with new-onset disease compared with that in...
A potential role of Staphylococcus aureus in bullous pemphigoid was explored by examining the colonization rate in patients with new-onset disease compared with that in age- and sex-matched controls. S. aureus colonization was observed in 85% of bullous pemphigoid lesions, 3-6-fold higher than the nares or unaffected skin from the same patients (P ≤ 0.003) and 6-fold higher than the nares or skin of controls (P ≤ 0.0015). Furthermore, 96% of the lesional isolates produced the toxic shock syndrome toxin-1 superantigen, and most of these additionally exhibited homogeneous expression of the enterotoxin gene cluster toxins. Toxic shock syndrome toxin-1‒neutralizing antibodies were not protective against colonization. However, S. aureus colonization was not observed in patients who had recently received antibiotics, and the addition of antibiotics with staphylococcal coverage eliminated S. aureus and resulted in clinical improvement. This study shows that toxic shock syndrome toxin-1‒positive S. aureus is prevalent in bullous pemphigoid lesions and suggests that early implementation of antibiotics may be of benefit. Furthermore, our results suggest that S. aureus colonization could provide a source of infection in patients with bullous pemphigoid, particularly in the setting of high-dose immunosuppression.
Topics: Anti-Bacterial Agents; Bacterial Toxins; Enterotoxins; Humans; Pemphigoid, Bullous; Staphylococcal Infections; Staphylococcus aureus; Superantigens
PubMed: 34606884
DOI: 10.1016/j.jid.2021.08.438 -
Journal of Immunology Research 2024Superantigens are virulence factors secreted by microorganisms that can cause various immune diseases, such as overactivating the immune system, resulting in cytokine... (Review)
Review
Superantigens are virulence factors secreted by microorganisms that can cause various immune diseases, such as overactivating the immune system, resulting in cytokine storms, rheumatoid arthritis, and multiple sclerosis. Some studies have demonstrated that superantigens do not require intracellular processing and instated bind as intact proteins to the antigen-binding groove of major histocompatibility complex II on antigen-presenting cells, resulting in the activation of T cells with different T-cell receptor V and subsequent overstimulation. To combat superantigen-mediated diseases, researchers have employed different approaches, such as antibodies and simulated peptides. However, due to the complex nature of superantigens, these approaches have not been entirely successful in achieving optimal therapeutic outcomes. CD28 interacts with members of the B7 molecule family to activate T cells. Its mimicking peptide has been suggested as a potential candidate to block superantigens, but it can lead to reduced T-cell activity while increasing the host's infection risk. Thus, this review focuses on the use of drug delivery methods to accurately target and block superantigens, while reducing the adverse effects associated with CD28 mimic peptides. We believe that this method has the potential to provide an effective and safe therapeutic strategy for superantigen-mediated diseases.
Topics: CD28 Antigens; Antibodies; Antigen-Presenting Cells; Peptides; Superantigens
PubMed: 38268531
DOI: 10.1155/2024/2313062