I. BACTERIAL PATHOGENESIS
C. VIRULENCE FACTORS THAT DAMAGE THE HOST
2. Producing Harmful Exotoxins
a. Type I Toxins (Superantigens)
The overall purpose of this Learning Object is:
1) to learn how Type I toxins (superantigens)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 toxins, often proteins in nature, secreted from a living bacterium but also released upon bacterial lysis. In addition, some bacteria use a type 3 secretion system or a type 4 secretion system to inject toxins directly into human cells. There are three main types of exotoxins:
1. superantigens (Type I toxins),
2. exotoxins that damage host cell membranes (Type II toxins)
3. A-B toxins and other toxin that interfere with host cell function (TypeII I toxins).
We will now look at superantigens.
The Ability to Produce Harmful Exotoxins
a. Type I toxins (Superantigens)
Superantigens (def) are unusual bacterial toxins that interact with exceedingly large numbers of T4-lymphocytes (def). They bind to the surface of the target cell but do not enter the cell.
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. The normal response to a conventional antigen results in the activation of maybe 1 in 10,000 T-lymphcytes; superantigens can activate as many as 1 in 5 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.
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 (the group A beta streptococci). S pyogenes produces a number of SPEs that are cytotoxic, pyrogenic (def), enhance the lethal effects of endotoxins, and contribute to cytokine-induced inflammatory damage. SPEs are responsible for causing toxic shock-like syndrome (TSLS) whereby excessive cytokine production leads to fever, rash, and triggering the shock cascade. The SPEs also appear to be responsible for inducing necrotizing fasciitis (def), a disease that can destroy the skin, fat, and tissue covering the muscle (the fascia). SPE B is also a precursor for a cysteine protease that can destroy muscles tissue.
- 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.
- ETEC enterotoxin, produced by enterotoxogenic E. coli (ETEC) (inf), one of the most common causes of traveler's diarrhea.
E-Medicine article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
Kaiser's Microbiology Home Page
Copyright © Gary E. Kaiser
All Rights Reserved
Updated: May, 2011
Please send comments and inquiries to Dr. Gary Kaiser