Antisepsis, Disinfection, and Sterilization. Gerald E. McDonnell
Bacterial toxins are categorized as exotoxins when they are actively produced and released from the bacterial cell during growth and as endotoxins when they are a normal part of the cell wall structure but are toxic when released following damage to the cell wall or on cell death.
The most widely studied bacterial exotoxins are proteins (ranging in size from 50 to 1,000 kDa) that are released from actively growing gram-positive and gram-negative bacteria. As proteins, they are generally heat sensitive, although some have been shown to survive heat treatment processes. Many exotoxins are potent poisons at relatively low concentrations and are important virulence factors in bacterial diseases, such as anthrax, tetanus, cholera, and food poisoning. Their toxic effects can include cell damage (AB toxins), cell lysis (cytotoxic toxins), and an inflammatory response (superantigen toxins). Examples of exotoxins and their effects on host cells are given in Table 1.16.
By definition, endotoxins can be any cell-bound toxin that is released upon cell damage or cell death, although the term is generally used to refer to the LPS component of the cell walls of gram-negative bacteria, including E. coli, Salmonella, Shigella, and Pseudomonas (see section 1.3.4.1). LPS contains a lipid portion (known as lipid A) that forms part of the external surface of the outer membrane, which is linked to an external polysaccharide (containing a core and an O-polymer of sugars) (Fig. 1.15). The exact fatty acid and sugar structures of LPS vary among gram-negative species. In general, the polysaccharide can contain various types of sugars and the lipid A portion consists of fatty acids attached to a disaccharide of N-acetylglucosamine phosphate.
TABLE 1.16 Common examples of bacterial exotoxins
| Type | Example | Microorganism | Effects |
| AB toxins (component toxins that cause cell damage) | Diphtheria toxin | Corynebacterium diphtheriae | Inhibition of protein synthesis |
| Tetanus and botulism toxins | Clostridium tetani, Clostridium botulinum | “Neurotoxins”; block neurotransmitters | |
| Cholera toxin | Vibrio cholerae | “Enterotoxin”; secretion of fluids from small intestine | |
| Cytotoxic toxins (cause cell lysis) | α, β, and γ toxins | Corynebacterium perfringens | Cell lysis, including damage to cell membrane |
| α toxin | Staphylococcus aureus | Cell lysis | |
| Superantigen toxins (cause an immunological response and inflammation) | Toxic shock syndrome toxin | Staphylococcus aureus | Septic shock |
| Erythrogenic toxin | Streptococcus pyogenes | Scarlet fever rash |
Endotoxins can have a variety of biological activities when introduced directly into the blood and are therefore an important consideration in various pharmaceutical, medical-device, and water purification applications. LPS is pyrogenic (fever causing) and induces an inflammatory response, which can lead to septic shock, diarrhea, and, under some circumstances, death. The polysaccharide component is considered responsible for fever and inflammation, while the lipid A component is linked to the toxicity effect on host cells. Overall, the toxic effects of LPS are considered to be less than those of exotoxins. Endotoxins are notably heat resistant.
FIGURE 1.15 The general structure of lipopolysaccharide. The lipid A component is integrated into the outer membrane of the gram-negative cell wall, with the polysaccharide portion extending to the outside of the cell.
Mycotoxins are produced by fungi, in particular, molds like Aspergillus, Fusarium, Stachybotrys, Penicillium, and Chaetomium. They are usually produced during the late exponential and/or stationary phase of growth and, like other secondary metabolites (e.g., antibiotics), provide competitive advantages to the fungus in its environment. They can be associated with the vegetative mold, its spores, or surrounding mold growth. Most of these toxins are chemical in nature, and they include aflatoxins, ochratoxins, trichothecenes, and gliotoxins; an example of a fungal aflatoxin is shown in Fig. 1.16.
FIGURE 1.16 Typical fungal aflatoxin structure.
Mycotoxins also have multiple effects on target cells, including membrane damage, cell death, and free-radical damage. Aflatoxins have been particularly associated with food and feed (grain) contamination and have been shown to be carcinogenic. Some fungal cell wall components (like β-1,3-glucan) are also considered toxins and can cause allergic reactions, including coughing and other respiratory effects.
Many algae also produce toxins, which are often associated with contaminated water. These include hepatoxins (in particular, from blue-green algae), neurotoxins, cytotoxins, and endotoxins (similar to gram-negative bacteria, the LPS from the outer membrane of the algal cell wall).
1.4 GENERAL CONSIDERATIONS
1.4.1 Microbial Resistance
Different types of microorganisms vary in their responses to antiseptics, disinfectants, and sterilants. This is hardly surprising, in view of their different