Information from CDC
Biological Toxins. Biological toxins (also referred to as biotoxins) are nonliving toxic proteins that are naturally produced by many different types of living organisms. Biotoxins are:
Bacterial Toxins: Friends or Foes?
Clare K. Schmitt, Karen C. Meysick, and Alison D. O'Brien
Since diphtheria toxin was isolated by Roux and Yersin in 1888, microbial toxins have been recognized as the primary virulence factor(s) for a variety of pathogenic bacteria. Bacterial toxins have been defined as "soluble substances that alter the normal metabolism of host cells with deleterious effects on the host". Indeed, the major symptoms associated with disease caused by Corynebacterium diphtheriae (diphtheria), Bordetella pertussis (whooping cough), Vibrio cholerae (cholera), Bacillus anthracis (anthrax), Clostridium botulinum (botulism), Clostridium tetani (tetanus), and enterohemorrhagic Escherichia coli (bloody diarrhea and hemolytic uremic syndrome) are all related to the activities of the toxins produced by these organisms. With the recognition of the central role of toxin in these and other diseases has come the application of inactive toxins (toxoids) as vaccines. Such toxoid vaccines have had an important positive impact on public health.
In this review, we provide a summary overview (Table) of a variety of bacterial toxins categorized according to mode of action: damaging cell membranes, inhibiting protein synthesis, activating second messenger pathways, inhibiting the release of neurotransmitters, or activating the host immune response. We also describe in detail seven toxins: Staphylococcus aureus -toxin, Shiga toxin (Stx), cytotoxic necrotizing factor type 1 (CNF1), E. coli heat-stable toxin (ST), botulinum and tetanus neurotoxins, and toxic-shock syndrome toxin (TSST) produced by S. aureus. We emphasize these toxins because they are produced by emerging (Stx of enterohemorrhagic E. coli) or reemerging (-toxin of multidrug-resistant S. aureus) pathogens or illustrate different structures or modes of action (ST, CNF1, neurotoxins, and TSST).
When It Rains, It Pores
Many bacterial exotoxins have the capacity to damage the extracellular matrix or the plasma membrane of eukaryotic cells. The damage not only may result in the direct lysis of cells but also can facilitate bacterial spread through tissues. Toxins that mediate this cellular damage do so by either enzymatic hydrolysis or pore formation. Bacterial hyaluronidases, collagenases, and phospholipases have the capacity to degrade cellular membranes or matrices. Specific examples of these types of toxins include the -toxin of Clostridium perfringens, which has phospholipase C activity; Streptococcus pyogenes streptokinase, which can hydrolyze plasminogen to plasmin and dissolve clots; and the clostridial collagenases. Pore-forming toxins, as the name suggests, disrupt the selective influx and efflux of ions across the plasma membrane by inserting a transmembrane pore. This group of toxins includes the RTX (repeats in toxin) toxins from gram-negative bacteria, streptolysin O produced by S. pyogenes, and the S. aureus -toxin (described below).
S. aureus -toxin can be considered the prototype of oligomerizing pore-forming cytotoxins. The -toxin gene resides as a single copy on the chromosome of most pathogenic S. aureus strains, and its expression is environmentally regulated at the transcriptional level by the staphylococcal accessory gene regulator (agr) locus. The -toxin is synthesized as a 319 amino acid precursor molecule that contains an N-terminal signal sequence of 26 amino acids. The secreted mature toxin, or protomer, is a hydrophilic molecule that lacks cysteine residues and has a molecular mass of approximately 33 kDa. Recently, the crystallographic structure of the fully assembled -toxin pore was solved. On the plasma membrane, seven toxin protomers assemble to form a 232 kDa mushroom-shaped heptamer comprising three distinct domains (Figure 1A). The cap and rim domains of the -toxin heptamer are situated at the surface of the plasma membrane, while the stem domain serves as the transmembrane channel.
Alpha-toxin is cytolytic to a variety of cell types, including human monocytes, lymphocytes, erythrocytes, platelets, and endothelial cells. For -toxin to damage cellular membranes, three sequential events are required. Toxin protomers must first bind to target membranes by either unidentified high-affinity receptors or through nonspecific absorption to substances such as phosphotidylcholine or cholesterol on the lipid bilayer. Second, membrane-bound protomers must oligomerize into a nonlytic prepore heptamer complex. Third, the heptamer must undergo a series of conformational changes that create the stem domain of the toxin, which is then inserted into the membrane. The -toxin pore allows the influx and efflux of small molecules and ions that eventually lead to the swelling and death of nucleated cells and the osmotic lysis of erythrocytes. Pore formation has also been shown to trigger secondary events that could promote development of pathologic sequelae. These events include endonuclease activation, increased platelet exocytosis, release of cytokines and inflammatory mediators, and production of eicosanoids. Several animal models have demonstrated that -toxin is required for S. aureus virulence in these systems; however, the precise role of -toxin in staphylococcal diseases in humans remains unclear.
Stop, in the Name of Toxin
A second class of toxins intoxicates target cells by inhibiting protein synthesis. Substrates for toxins in this group are elongation factors and ribosomal RNA. Diphtheria toxin and Pseudomonas exotoxin A act by ADP-ribosylating elongation factor 2 (EF2). The modified EF2 is no longer able to function in protein synthesis. Stxs, also called verotoxins, are produced by Shigella dysenteriae serotype 1 and the emerging pathogens designated Stx-producing E. coli (STEC). Stxs inactivate ribosomal RNA (by a mechanism described below) so that the affected ribosome can no longer interact with elongation
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Disclaimer: This information is intended as a guide only. This information is offered to you with the understanding that it not be interpreted as medical or professional advice. All medical information needs to be carefully reviewed with your health care provider.