I. BACTERIAL PATHOGENESIS

C. VIRULENCE FACTORS THAT DAMAGE THE HOST

2. Producing Harmful Exotoxins

a. Superantigens (Type I Toxins)

The overall purpose of this Learning Object is:
1) to learn how superantigens (Type I toxins) are able to cause harm to the body; and
2) to introduce several examples of medically important bacteria that produce superantigens.

LEARNING OBJECTIVES FOR THIS SECTION

In this section on Bacterial Pathogenesis we are looking at virulence factors that damage the host. Virulence factors that damage the host include:

1. The ability to produce cell wall components (Pathogen-Associated Molecular Patterns or PAMPs) that bind to host cells causing them to synthesize and secrete inflammatory cytokines and chemokines;

2. The ability to produce harmful exotoxins.

3. The ability to induce autoimmune responses.

We are currently looking at the ability of bacteria to produce harmful exotoxins.

Exotoxins (def) are protein toxins usually secreted from a living bacterium but also released upon bacterial lysis. There are three main types of exotoxins:

1. superantigens (Type I toxins),

2. A-B toxins and other toxin that interfere with host cell function (Type III toxins), and

3. exotoxins that damage host cell membranes (Type II toxins).

We will now look at superantigens.

Superantigens (Type I toxins)

Superantigens (def) are unusual bacterial toxins that interact with exceedingly large numbers of T4-lymphocytes (def) . Conventional antigens (def) are engulfed by antigen presenting cells (APCs) (def), degraded into epitopes (def), bind to the peptide groove of MHC-II molecules (def), and are put on the surface of the APC (see Fig. 1). Here they are recognized by specific T4-lymphocytes having a TCR (def) with a corresponding shape (see Fig. 2).

Superantigens, however, bind directly to the outside of MHC-II molecules and activate large numbers of T4-lymphocytes (see Fig. 3). This activation of very large numbers of T4-lymphocytes results in the secretion of excessive amounts of a cytokine called interleukin-2 (IL-2) as well as the activation of self-reactive T-lymphocytes. Production of high levels of IL-2 can result in circulation of IL-2 in the blood leading to symptoms such as fever, nausea, vomiting, diarrhea, and malaise. However, excess stimulation of IL-2 secretion can also lead to production of other cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), inflammatory chemokines such as IL-8, and platelet-activating factor (PAF), and can lead to the same endothelial damage, acute respiratory distress syndrome, disseminated intravascular coagulation, shock, and multiple organ system failure seen above with LPS and other bacterial cell wall factors. Activation of self-reactive T-lymphocytes can also lead to autoimmune attack.

For More Information: The Shock Cascade from Unit 2

For More Information: Inflammation from Unit 4

The following are examples of superantigens.

• Toxic shock syndrome toxin-1 (TSST-1), produced by some strains of Staphylococcus aureus. This exotoxin causes toxic shock syndrome (TSS). Excessive cytokine production leads to fever, rash, and shock.

• Streptococcal pyrogenic exotoxin (Spe), produced by rare invasive strains and scarlet fever strains of Streptococcus pyogenes (group A beta streptococci). This exotoxin causes toxic shock-like syndrome (TSLS). Excessive cytokine production leads to fever, rash, and shock.

Highlighted Bacterium: Streptococcus pyogenes Click on this link, read the description of Streptococcus pyogenes, and be able to match the bacterium with its description on an exam.

• Staphylococcal enterotoxins (SE), produced by many strains of Staphylococcus aureus. These exotoxins cause staphylococcal food poisoning. Excessive Il-2 production results in fever, nausea, vomiting,and diarrhea. The vomiting may also be due to these toxins stimulating the vagus nerve in the stomach lining that controls vomiting.

• QUIZ YOURSELF ON THIS SECTION

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Updated: July, 2007
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