CBRNE - Staphylococcal Enterotoxin B 

Toxins are poisons produced by living organisms. Staphylococcal enterotoxin B (SEB) is an exotoxin excreted by the Staphylococcus aureus bacterium. Staphylococcus species thrive and produce toxins in unrefrigerated meats, dairy, and bakery products. SEB normally exerts its effect on the intestines and, therefore, is termed an enterotoxin. Not all toxins result in a lethal outcome, but they may result in significant morbidity.^[1]

Staphylococcal enterotoxin B (SEB) is the toxin most commonly associated with classic food poisoning. It has also been demonstrated to cause a nonmenstrual toxic shock syndrome (TSS).^[2] SEB has been studied as a potential biological warfare agent because it can easily be aerosolized; it is very stable; and it can cause widespread systemic damage, multiorgan system failure, and even shock and death when inhaled at very high dosages. However, SEB is classified as an incapacitating agent because in most cases aerosol exposure does not result in death but in a temporary, though profoundly incapacitating, illness lasting as long as 2 weeks.^[3]

Source

Staphylococcal enterotoxin B (SEB) is 1 of 7 originally identified enterotoxins produced by certain strains of the coagulase-positive S aureus bacteria, a gram-positive cocci that form clumps. Research has elucidated the structures of numerous enterotoxin-like superantigens, with two new enterotoxins, now known as SES and SET, just discovered in 2008.^[4]S aureus is known to colonize the nasal passages and axillae in humans.

Structure

Staphylococcal enterotoxin B (SEB) consists of 239 amino acid residues and has a molecular weight of 28 kd. It is 1 of the 6 least antigenically distinct enterotoxin proteins that have been identified (A, B, C, D, E, G). SEB has 2 distinct tightly "packed" domains that have a very complex tertiary structure. It is this compact structure that enables SEB to be highly resistant to proteases, including trypsin, chymotrypsin, and papain, which are all found in the intestinal lumen.

Properties

Staphylococcal enterotoxin B (SEB) is a relatively stable compound that is easily soluble in water. It is moderately resistant to temperature fluctuations and can withstand boiling at 100 º C for several minutes. In the freeze-dried state, SEB can be stored for more than a year. For aerosol exposures, the effective dose, or ED₅₀ (dose capable of incapacitating 50% of the exposed human population), is 0.0004 mcg/kg, and the lethal dose, or LD₅₀, is 0.02 mcg/kg.^[5]

Mechanism of toxicity

Many of the effects of staphylococcal enterotoxin B (SEB) are mediated stimulation of T lymphocytes by the host's immune system. The toxin binds directly to the major histocompatability complex (MHC) class II proteins on target cells, subsequently stimulating the proliferation of large numbers of T lymphocytes. SEB is a "bacterial superantigen" because it can form a "bridge" between the MHC II on the antigen presenting cells and the T-cell receptors on both CD4 and CD8 T cells, thereby bypassing the normal antigen processing and presenting mechanism. This bridging effect causes the release of massive amounts of cytokines, specifically interleukin 2 (IL-2), tumor necrosis factor β (TNF-β), and interferons.

The cytokines not only cause a recruitment of additional inflammatory cells but there is a relative deficient activation of negative counter-regulatory feedback loops. Taken together, the body's own inflammatory response most likely mediates many of the toxic effects of SEB. Ingestion of SEB produces profound gastrointestinal (GI) symptoms, including anorexia, nausea, vomiting, and diarrhea, which are believed to be mediated through the release of cytokines from T cells in the lamina propria of the intestines. Animal studies have shown that the severe pulmonary edema associated with aerosol exposure is likely secondary to T-cell proliferation within the respiratory mucosa and not the toxin itself.^{[1, 3, 6]}

Frequency

United States

The actual incidence of SEB-related food poisoning is unknown; many cases are so mild that patients do not seek treatment. Additionally, diagnoses in the emergency department are usually presumptive, and a number of other diseases may mimic SEB-induced gastroenteritis.

Mortality/Morbidity

The gastrointestinal form of staphylococcal enterotoxin B (SEB) toxicity, while potentially debilitating for short durations, is rarely fatal with adequate hydration.

No data are available regarding the mortality and morbidity of inhalational SEB exposure.

Age

Very young and elderly persons are likely the most susceptible to a complicated course.