What are Microbial Toxins?

Microbial Toxin and impact on   

         Human Health.

What are microbial toxins?

Microbial toxins are toxins produced by microorganisms, including bacteria and fungi. Microbial toxins promote infections and diseases by directly damaging host tissues and by disabling the immune system. Some bacterial toxins, such as Botulinum neurotoxins, are the most potent natural toxins known.

The term “microbial toxin” is usually reserved by microbiologists for toxic substances produced by microorganisms that are of high molecular weight and have antigenic properties; toxic compounds produced by bacteria that do not fit these criteria are usually referred to simply as poisons. Many of the former are proteins or mucoproteins and may have a variety of enzymatic properties. They include some of the most toxic substances known, such as tetanus toxin, botulinum toxin, and diphtheria toxin.

EXOTOXINS

Exotoxin producing bacteria

1.  Corynebacterium diphtheriae. Strains that carry a temperate bacteriophage are toxigenic causes diphtheria. Exotoxin inhibits protein synthesis and causes cell death. Causes diphtheria.

2.  Clostridium tetani. Exotoxin blocks action of inhibitory neurones of spinal cord. Causes tetanus.

3.  Clostridium perfringens. (a) Causes gas gangrene. Exotoxin (alpha toxin) has lacithinase activity and thereby causes cell death, (b) Enterotoxin causes hyper secretion of water and electrolytes in diarrhoea.

4.   Clostridium botulinum. Exotoxin causes paralysis of deglutination and respiratory muscles. It blocks release of acetylcholine of synapses and neuromuscular junctions. Causes botulism.

5.  Vibrio cholerae 01 and 0139. Enterotoxin (Exotoxin) causes hyper secretion of water and electrolytes within gut in diarrhoea.

6.  Enterotoxigenic E. coll. Produce enterotoxin (LT- heat labile exotoxin) causes hypersecretion of water and electrolytes within gut.

7.  Shigella dysenteriae type 1 (Shiga bacillus). Exotoxin causes acute inflammation.

8.  Staphylococcus aureus- some strains : (a) Toxic shock syndrome toxin-1. Causes toxic shock syndrome. (b) Staphylococcal enterotoxin causes toxin type food poisoning and stimulates vomiting centre of brain.

9.  Streptococcus pyogenes. Pyrogenic (Erythrogenic) exotoxin causes scarlet fever and toxic shock syndrome.

ENDOTOXINS

Endotoxins are the integral part of the cell walls of Gram-negative bacteria, and are liberated when bacteria are disintegrated (lysed). Cell wall of Gram negative bacteria contains lipopolysaccharides (LPS, endotoxin) which consists of : (1) Lipid A. This is the endotoxin and is the core, and (2) Polysaccharide form coat.

This is the antigen which can induce specific immunity. Physiological, pathological and clinical effects of endotoxins of different Gram negative bacteria are similar. These are :

1. Fever. The endotoxin acts on mononuclear phagocytes (monocytes/macrophages), with liberation of interleukin-1 (endogenous pyrogen). Interleukin-1 acts on thermoregulatory centre. Chill is due to widespread arteriolar and venular constriction.

2. Leucopenia occurs early with onset of fever. It may be followed by leucocytosis.

3. Hypoglycaemia. LPS enhances glycolysis in many cell types and can lead to hypoglycaemia.

4. Hypotension occurs early in Gram-negative bacteraemia.

5. Shock. 'Endotoxic' or 'septic' shock may develop in severe Gram-negative bacteraemia (See chapter 4).

6.   Activation of complement. Endotoxin activates complement system by alternative pathway.

7. Disseminated Intravascular Coagulation (DIC). DIC may occur in Gram negative bacteraemia. It is initiated on activation of factor XII (Hageman factor) of coagulation cascade by endotoxin which finally leads to conversion of fibrinogen to fibrin. Endotoxin leads platelets to adhere on vascular endothelium. Endotoxin can activate plasminogen to plasmin which acts on fibrin producing fibrin-split products. Shwartzman phenomenon is taken as a specialized form of DIC.

8. Death may occur due to shock and/or DIC.

Characteristics and Differences of Exotoxins and EndotoxinsEndotoxin:

1.  Integral part of the cell wall of Gram-negative bacteria. Released on bacterial death and in part during growth. Release is not required for biologic activity.

2.  Formed only by Gram-negative bacteria

3.  Lipopolysaccharides. Lipid A portion is responsible for toxicity.

4.  No specific receptor.

5.  Moderately toxic. Fatal to animals in large doses.

6.  Relatively heat stable. Toxicity is not destroyed above 60°C for hours.

7.  Weakly antigenic. Antibodies are protective.

8.  Not converted to toxoid.

9.  Synthesis directed by chromosomal genes.

10. Usually produce fever in the host by release of interleukin-1 and other mediators..]

Exotoxins:

1. Excreted by living cells

2.  Produced by Gram-positive and Gram-negative bacteria

3.  Polypeptides

4.  Usually bind to specific receptors on cells

5.  Highly toxic. Fatal to animals in very small doses

6.  Relatively heat labile. Toxicity destroyed over 60°C

7.  Highly antigenic. Stimulate formation of antitoxin. Antitoxin neutralizes the toxin

8.  Converted to toxoid by formalin. Toxoid is nontoxic but antigenic. Toxoids are used to immunize, e.g. tetanus toxoid

9.  Usually controlled by extra-chromosomal genes, e.g. plasmids, phage gene

10. Usually do not produce fever in the host.

Role of Microbes in Human Health 

Microbes are ubiquitous and have ecological interactions with almost all life forms. Likewise, humans invariably engage in host-microbial interactions that could induce short-term or long-term effects. Some of these long-term crossover interactions have allowed successful colonization of microbes within or on the human body, collectively known as the human microbiome or human microbiota.

The human microbiome is identified as playing a key role in various physiological processes like digestion, immunity, defense, growth, and development. Any dysbiosis in the human microbiome structure could induce the onset of various metabolic or physiological disorders. Cumulatively, the human microbiome is considered as a virtual human organ that is essential for host survival. Additionally, short-term biological interactions of the host and microbes have exposed microbes to the human cellular system. This exposure could have allowed the microbes to invade human cells for their growth and reproduction-induced onset of various infectious diseases.

Human and microbes

The study of human microbiome diversity started with Antonie Van Leeuwenhoek, when he had a comparison of his oral and fecal microbiota in 1680s. He found that different microbes are present in different habitats and also different microbes are present in healthy and diseased person . There is a growing evidence that any change in microbiota composition leads to several metabolic diseases including obesity, diabetes and cardiovascular.

 Different parts of intestinal tract have different composition of microbes and it varies according to age, weight, site and diet. Composition of microbiota in gut alters by nutrition, drugs, diet and genetic background and lifestyle. Microbiota regulates metabolic and physiological mechanisms by producing metabolites. It has been found out that different species of microbiota in gut works under same metabolic pathway . Qualitative and quantitative alteration in gut microbiota leads to dysbiosis by consuming antibiotics, physical and psychological stress . Recent studies shows evidence regarding change in composition by urban and rural environment, affects skin (allergic symptoms) of particular organisms. Age alter the environmental effects on individual such as alter microbiota variations in skin between children and teenager cause skin allergies . Microbiome structure varies in respect of host anatomical and physiological sites. Normally, flora found in/on the body surface in stable condition to compete with pathogenic microbes in environment or those microbes entered in specific body parts.

However a number of factors like change in diet, variable host immune response, fluctuating environmental conditions like pH, oxygen saturation, ionic strength, etc., could induce microbial dysbiosis and induce microbial community dynamics. These microbial community dynamics couldinduce favorable conditions for growth of earlier dormant pathogenic microbes and result in onset of infectious diseases .

Conclusion

Microbes have been identified to play a vital role in human health and diseases. Physiological characterization of these microbes and defining their functional molecular machinery could enable us to develop potential therapeutic and diagnostic targets. Additionally, holistic overview of human microbiome structure, human microbe interactions and role of microbes in human health and diseases are the key areas of current research focus. In-depth information about host microbial interaction in human health and diseases could enable to identify causative factors for development of host physiological/metabolic disorders. Current book comprises of various chapters defining a relation among human and microbes in health and diseases.

REFERENCES……

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? https://link.springer.com/chapter/10.1007/10_2015_5008

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