BACTERIAL TOXINS

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Toxins are specific microbial products or secretions which at very low concentrations can act specifically on the cells and tissues of other organisms including humans to cause a local or systemic damage. Toxins which are found in both Gram-positive and Gram-negative bacteria help to increase the pathogenicity and virulence nature of a given pathogen once they have gained entry into the body or cells of their host. It is noteworthy that not all microbial products are regarded as toxins as some may be beneficial and even harmful to other microorganisms. Typical examples include antibiotics and bacteriocins produced by some bacteria, and are beneficial to man and animals. The ability of pathogenic bacteria to produce toxin and the potency or effectiveness of the toxin is an important factor in the capability of the invading pathogenic microbe to initiate or cause a disease in the host. Bacterial toxins are poisonous substances that increase the pathogenicity of the pathogenic microbe in vivo.

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Toxin production in pathogenic bacteria is an important component of bacterial infection, and they help to further the disease process of the pathogenic microbe in the host. However, the pathogenicity and virulence of infections caused by pathogenic viruses, fungi and other pathogens have not been associated with toxin production as is the case in pathogenic bacteria – where this phenomenon (i.e., toxin production) is an important characteristic component which help to enhance the damaging effects of the invading pathogenic bacterium in their human host. Toxins produced by bacteria may be secreted into the surrounding environment of the organism (these are known as exotoxins) or it may be retained within the bacterial cells (these are known as endotoxins). Toxins produced by bacterial pathogens alter the normal metabolic activity of their host cells, and in turn cause poisonous or harmful effects which sicken the host. When heated and treated with acids, exotoxins lose their toxicity, and are transformed to toxoids which have anti-toxin effect and can be used to protect human hosts from the negative effects of the toxins. This is one beneficial effect or use of the toxins produced by pathogenic bacteria.  

Toxoids (which are protective vaccines) are used as important protection against diseases caused by bacterial toxins in a host. Endotoxins do not produce toxoids because they are rather heat stable than exotoxins which are heat labile. Exotoxins are mostly produced by Gram-positive and Gram-negative bacteria while endotoxins are produced mostly by Gram-negative bacteria, and they rarely stimulate antibody production in a host.

  • EXOTOXIN PRODUCING BACTERIA

Exotoxins are extracellular toxins produced by living bacterial cells. They are protein molecules excreted by growing bacteria into the surrounding medium where the bacterium grows or into the tissues, cells and circulatory system of their human host. Exotoxins are diffusible in nature, and they are produced by both Gram-positive and Gram-negative bacteria. They are known to occasionally bind specifically to receptors on the surfaces of their host cells, and they can be internalized by cells due to their diffusibility. Bacterial exotoxins exert their deleterious effects in the host through a variety of mechanisms such as protein synthesis inhibition, inhibition of nerve synapse functions, membrane transport disruption, and destruction of host cell’s plasma membrane. Some exotoxins can also act as superantigens by over-stimulating the immune response of the host against the invading bacterium. Exotoxins may be classified into different categories usually on the basis of their site of action as:

  • Enterotoxins: which are found in the intestinal mucosa where they cause a series of gastrointestinal infections (e.g., in the pathogenesis of Vibrio cholerae).
  • Neurotoxins: which occur in nerve tissues where they cause neurological damages (e.g., in the pathogenicity of Clostridium tetani).
  • Cytotoxins: which are normally found in the general tissues of the body where they cause a series of local and systemic damages (e.g., in the pathogenicity of Staphylococcus aureus).

CHARACTERISTICS OF EXOTOXINS

Bacterial exotoxins are known to exhibit some of the following features:

  • Exotoxins do not usually produce fever in their host.
  • They are highly immunogenic (i.e., antigenic), and thus can stimulate the production of antitoxins (which are neutralizing antibodies that switches off the deleterious effects of toxins in vivo).
  • They are heat-labile, and are inactivated at 60-80oC.
  • Exotoxins are used in the production of toxoids (when heated with acids or formalin) which activates the production of antitoxins in vivo.
  • They are produced by both Gram-positive and Gram-negative bacteria.
  • Exotoxins are not integral parts of the bacterial cell wall, and their production is usually controlled by extrachromosomal DNA (i.e., plasmids) in the bacterium.
  • They are extremely toxic in small amounts.

PATHOGENIC BACTERIA THAT PRODUCE EXOTOXINS

Some members of exotoxin-producing bacteria include:

  • Corynebacterium diphtheria – produces diphtheria toxin that kills cells and cause diphtheria.
  • Clostridium tetani – produces tetanus toxin (tetanospasmin) that causes muscle spasm (tetanus).
  • Clostridium botulinum – produces botulinum toxin that causes botulism.
  • Clostridium perfringens – produces alpha toxin that causes gas gangrene.
  • Clostridium difficile – produces enterotoxin that causes haemorrhagic diarrhea.
  • Vibrio cholerae – produces cholera toxin that causes cholera.
  • Staphylococcus aureus – produces enterotoxin in diary foods that causes food poisoning. S. aureus also produce toxic shock syndrome toxin-1 (TSST-1) which causes toxic shock syndrome in people infected with this strain of Staphylococcus.  
  • Streptococcus species – produces fever-causing toxins. Streptococcus toxins can also produce erythromatous rash on the skin.
  • Enterotoxigenic Escherichia coli (ETEC) – produces exotoxins that causes traveler’s diarrhea.
  • Shigella dysenteriae ­– produces shiga toxins that causes diarrhea. 
  • Bacillus anthracis – produces anthrax toxin that causes anthrax.
  • ENDOTOXIN-PRODUCING BACTERIA

Endotoxins are microbial toxins which are produced only on cell lysis i.e., on cell death. They are lipopolysaccharide (LPS) components of the outer membrane of Gram-negative bacteria. Endotoxins produce their effect in a host by activating the complement system by the alternative pathway. They also activate the production of macrophages and B cells, and exotoxins are unique because they are pyrogenic in action (i.e., they produce fever in their host). Endotoxins which are normally produced by dead bacterial cells can cause bacterial sepsis (shock) and intravascular coagulation in a host when they are produced in large amount by a pathogenic bacterium. But in small amounts, endotoxins produce a variety of effects which may include inflammation, vasodilation, fever and increased antibody production in vivo. Endotoxins are not manifested by living and intact bacterial cells but are only secreted when the cells disintegrate. In the laboratory, the Limulus Amoebocyte Lysate (LAL) test is used to assay the levels of endotoxin production in a host or a pharmaceutical product. Endotoxins are also known as LPS as aforesaid, and they are divided into three (3) components or regions viz:

  1. Lipid A
  2. Sugar core
  3. O antigen

The sugar core and O antigen are both the carriers of lipid A which is the biologically active component of LPS (endotoxins).

CHARACTERISTICS OF ENDOTOXINS

Bacterial endotoxins are known to exhibit some of the following features:

  • They are mainly produced by dead Gram-negative bacteria. 
  • Endotoxins are heat stable, and can withstand temperatures as high as 60oC.
  • They are toxic both at low and high dosages, but their effect are mostly observed in a host at a high concentration.
  • Endotoxins are weakly immunogenic, and thus cannot produce antitoxins.
  • They produce systemic effects such as fever and shock in a host.
  • Their secretion is directed by chromosomal DNA.
  • Endotoxins are fever-producing toxins, and they cause fever in their host through the production of interleukin-1 and other immunological mediators such as cytokines.
  • They are integral parts of the cell wall of Gram-negative bacteria.

Further reading

Brooks G.F., Butel J.S and Morse S.A (2004). Medical Microbiology, 23rd edition. McGraw Hill Publishers. USA.

Gilligan P.H, Shapiro D.S and Miller M.B (2014). Cases in Medical Microbiology and Infectious Diseases. Third edition. American Society of Microbiology Press, USA.

Madigan M.T., Martinko J.M., Dunlap P.V and Clark D.P (2009). Brock Biology of Microorganisms, 12th edition. Pearson Benjamin Cummings Inc, USA.

Mahon C. R, Lehman D.C and Manuselis G (2011). Textbook of Diagnostic Microbiology. Fourth edition. Saunders Publishers, USA.

Patrick R. Murray, Ellen Jo Baron, James H. Jorgensen, Marie Louise Landry, Michael A. Pfaller (2007). Manual of Clinical Microbiology, 9th ed.: American Society for Microbiology.

Wilson B. A, Salyers A.A, Whitt D.D and Winkler M.E (2011). Bacterial Pathogenesis: A molecular Approach. Third edition. American Society of Microbiology Press, USA.

Woods GL and Washington JA (1995). The Clinician and the Microbiology Laboratory. Mandell GL, Bennett JE, Dolin R (eds): Principles and Practice of Infectious Diseases. 4th ed. Churchill Livingstone, New York.

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