Related Experiment Video
Updated: May 20, 2026
12:27
Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
Staphylococcus aureus isolates encode variant staphylococcal enterotoxin B proteins that are diverse in
Petra L Kohler1, Seth D Greenwood, Suba Nookala
1Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Plos One
|July 21, 2012
Summary
Staphylococcus aureus superantigens (SAgs) cause toxic shock syndrome (TSS) by activating immune cells. New SEB variants exhibit diverse toxicities and immune cell activation profiles, suggesting potential therapeutic targets.
Area of Science:
- Immunology
- Microbiology
- Toxicology
Background:
- Staphylococcus aureus superantigens (SAgs) activate T cells and antigen-presenting cells (APCs), leading to massive cytokine release and potentially toxic shock syndrome (TSS).
- TSS toxin-1 (TSST-1), staphylococcal enterotoxin B (SEB), and staphylococcal enterotoxin C (SEC) are key SAgs causing staphylococcal TSS.
- While SEC variants are known, only one SEB variant was previously described.
Purpose of the Study:
- To investigate the genetic diversity of staphylococcal enterotoxin B (seb) genes in Staphylococcus aureus isolates.
- To characterize the functional differences of newly identified SEB variants.
- To assess the potential of a high-affinity Vβ-TCR as a therapeutic agent against SEB-mediated illnesses.
Main Methods:
- Sequencing of seb genes from over 20 S. aureus isolates to identify different alleles.
- Purification and examination of variant SEBs for their effects on rabbit splenocyte and human peripheral blood mononuclear cell proliferation in vitro.
- Assessment of variant SEB lethality in a rabbit model of TSS and their ability to activate T cell subsets.
- Testing the neutralizing capacity of a soluble, high-affinity Vβ-TCR against variant SEBs.
Main Results:
- At least five different seb alleles were identified, encoding SEB variants with amino acid substitutions outside known immune-cell binding regions.
- These SEB variants exhibited distinct abilities to induce splenocyte and peripheral blood mononuclear cell proliferation, varying in lethality in a rabbit TSS model.
- The variant SEBs also differed in their activation of specific T cell subsets.
- A high-affinity Vβ-TCR, previously designed to neutralize SEB1, effectively neutralized the variant SEBs.
Conclusions:
- Genetic variation in seb genes leads to functional differences in SEB variants, impacting immune cell activation and pathogenicity.
- The identified SEB variants display diverse profiles of immune cell proliferation, T cell activation, and lethality.
- A high-affinity Vβ-TCR demonstrates potential as a broad-spectrum therapeutic for SEB-mediated diseases.
Related Concept Videos
01:12Bacterial Toxins
Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
01:29Staphylococcal Skin Infections
Staphylococcus aureus is a Gram-positive coccus that resides harmlessly on the skin and mucous membranes of healthy individuals. When the skin barrier is breached, it can shift from a commensal to an opportunistic pathogen. This transition is facilitated by surface adhesins, such as clumping factor B and S. aureus surface protein G (SasG), which bind to structural proteins, including loricrin and cytokeratin, in the damaged epidermis. Protein A, another key factor, binds the Fc region of...
01:18Bacterial Gastroenteritis
Bacterial gastroenteritis, characterized by diarrhea, abdominal cramps, and vomiting, is often caused by ingestion of contaminated food or water and is frequently associated with pathogenic Escherichia coli strains. These microbes exploit two principal mechanisms to inflict disease.Shiga toxin–producing E. coli, also referred to as STEC—notably O157:H7—release Shiga toxins that target ribosomes, blocking protein synthesis. The B subunit of the toxin binds the host glycolipid receptor...
01:25Clinical Significance of Antibiotic Resistance
Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
01:31Defense Against Bacterial Pathogens
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:28Regulation of Bacterial Virulence
Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...