Role of Bacterial Endotoxins and Exotoxins in Development of Diseases - Coursework Example

Your University name Bacterial pathogenesis: Their Role in Development of Diseases Your Name [Pick the date] It is well known that bacteria have developed a number of different techniques in which it can cause diseases; once it has entered the body. Pathogenicity in bacteria may be associated with unique structural components of the cells, e.g. capsules, pili, lipopolysaccharides or active secretion of substances such as toxins that may produce damage to local tissues in addition to damage to distant tissues or protect the bacteria against host defenses. Table of Contents Table of Contents 2 Bacterial Pathogenesis: 3 Virulence factors: 4 1. Entry into the Host: 4 2. Invasiveness: Adhesion of the bacteria to host cell 5 3. Propagation of the organism 5 4. Bacterial toxins: 5 Production of Disease (Toxin-induced damage) 6 Classification of bacterial toxins based on the site of action: 7 Bacterial Protein Toxins 10 Description of the Mode of Action in some Bacterial Toxins: 11 Examples of Bacterial Toxins: 13 References: 16 Internet Sources: 16 Topic: Microbiology Title: Bacterial Endotoxins and Exotoxins: - Their Role in Development of Diseases Outline Page 1. Bacterial pathogenesis Page 1. Virulence factors Page 3. Classification of bacterial toxins based on the site of action Page 5. Classification of bacterial toxins based on the mode of action Page 6. Bacterial Protein Toxins Page 7. Description of the Mode of Action in some Bacterial Toxins Page 8. Examples of Bacterial toxins Bacterial Pathogenesis: The infectious process can be divided into five stages. 1- These stages begin with entry into the host cell with avoidance of host primary defences. 2- Then adhesion of the bacteria to host cell. 3- Followed by propagation of the organism 4- Finally terminate at damage to host cells by bacterial toxins or an inflammatory response to the host and evasion of host secondary defences. Virulence factors: The process of bacterial pathogenesis begins with the of production of virulence factors by the invading bacteria. Virulence factors are said to be molecules which are produced through secretion by the by a bacterium and are expressed from the bacterium into the host cell. Virulence factors enhance the pathogenicity of the bacterium within the host cell; that is, virulence factors enhance the ability of the bacterium to cause disease in the host organism into which it is expressed. The power of bacterium virulence factors to cause disease in the host organism is also facilitated by its ability to inhibit certain metabolic functions of the host organism. Some of the most important classes of these virulence factors are reviewed as follows: 1. Entry into the Host: The first step of the infectious process is the entry of the bacteria into the host through many different ports, such as, the respiratory tract, gastrointestinal tract; or via skin that has been punctured, cut or burned. In fact, bacteria that are covered by an outer polysaccharide capsule have a better chance of surviving inside the host. It is well known that bacterial capsules made of carbohydrate, form part of the outer structure of many bacterial cells including Neisseria meningitidis (causative agent of meningitis). It should be noted that capsules play important roles in immune evasion, as they inhibit phagocytosis, as well as protecting the bacteria whilst outside a host. 2. Invasiveness: Adhesion of the bacteria to host cell Invasiveness is facilitated by many bacterial enzymes; the most famous two are collagenase and hyaluronidase. These enzymes degrade components of the extracellular matrix of the host cell. The degradation of the extracellular matrix of the host cell wall provides the invading bacteria with easier access to the host cell surfaces. Inflammation, which is caused by bacterial invasion of the host cell, can be either pyogenic (involving pus formation) or granulomatous (having nodular inflammatory lesion). 3. Propagation of the organism The propagation of the invading pathogenic bacteria within the host cell is facilitated by degradation of the tissues within the organ of the host organism into which the pathogen has entered. Some pathogenic bacterial strains, such as Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa, produce a variety of enzymes which have the ability of causing damage to host tissues. Some of these enzymes are: hyaluronidase, which breaks down the connective tissue component hyaluronic acid; as well as a range of proteases and lipases; DNAses, which break down DNA and haemolysins which break down a variety of host cells, including red blood cells. 4. Bacterial toxins: Having entered into the cell matrix of the host organism, some bacteria pathogens cause disease by producing toxins which are poisonous to the host organism. Toxins are products of a pathogen that can destroy, or damage or deactivate one or more essential components of the host, thus allowing the pathogen to survive and increase within the infectious site. In fact, there are more than two hundred and twenty (220) known toxins produced by bacterial organisms. They can be classified into two main groups. These are Exotoxins and Endotoxins. According to Harvey et al: “Microbial pathogenicity refers to the disease-causing as a result of microorganism’s activities… Bacterial toxins are considered as the most important part in the development of bacterial infections in a host organism. In other words a major group of virulence factors are bacterial toxins (Harvey, Champe, & Fisher). Production of Disease (Toxin-induced damage) Also, according to Harvey, et al, Toxigenesis, or the ability to produce toxins, is an underlying mechanism by which many bacterial pathogens produce disease in their host organisms. It is well known that bacteria have developed a number of different techniques in which they can cause diseases; once they have succeeded in entering the body of their host organism. Thus, pathogenicity in bacteria may be said to be associated with unique structural components of the cells of the particular pathogenic bacteria. The unique structural components of pathogenic bacteria include capsules, some of which are: pili, lipopolysaccharides; or they may be active secretion of substances such as toxins, which may cause damage to local tissues in addition to damage to distant tissues within the same host organism; or may even protect the bacteria against defences put up by the host organism in its attempt to ward off the invading pathogenic bacteria. Toxic substances produced by bacteria may be transported by the vascular or lymphatic system of the host organism, and cause cytotoxic effects at tissue sites within the host organism which are far removed from the original point of invasion or growth of the pathogenic bacteria. (Harvey, Champe, & Fisher) Classification of bacterial toxins based on the site of action: 1. Exotoxins Exotoxins include a huge number of proteins, which are often enzymes that are concealed from the host cell and which are mostly, but not exclusively, produced by gram positive bacteria inside the cells being invaded and which do their damage (as with Endotoxins) upon being released from the cell of the pathogenic bacteria into the tissues of the host organism. It is well known that many Exotoxins have generalizable targets or sites of action, on the basis of which they are classifiable into three main categories. These three categories are: Cytotoxins, enterotoxins and neurotoxins. (microbiologybytes.com) According to Harvey et al: “These groups of toxins include some of the most poisonous sub-stances known. Exotoxins proteins have two types of polypeptide components; one is responsible for binding the protein to the host cell and the other one produce a toxic effect” (Harvey, pp. 12, 13). a. A neurotoxin is a kind of bacterial toxin that acts specifically on nerve cells (neurons), of the host organism into which the pathogenic bacteria has invaded; usually by interacting with membrane proteins of the host organism such as channels. For example, Botulin which is produced by Clostridium botulinum causing botulism, and the other neurotoxin Tetanospasmin, which when produced by Clostridium tetani causes the pathologic condition in the host organism, called tetanus. (Atlas, 1994, pp. 481,482) b. In case of Cytotoxins, they work to destroy host cells into which the invading bacteria have successfully penetrated. An example of this class of toxins is the alpha-toxin, which is produced by Clostridium perfringens. c. The class of toxin called Enterotoxins, are specially affect the cell lining the gastrointestinal tract in humans. The enterotoxins of Staphylococcus aureus and many of the toxins produced by Escherichia coli are examples of this kind of toxins. In addition the various food poisonings and diarrhoea in humans are usually caused by enterotoxins. 2. Endotoxins Most Endotoxins produced by pathogenic bacteria are located in the cell envelope, Endotoxins refer specifically to the lipopolysaccharides (LPS) or lipooligosaccharide (LOS) located in the outer membrane of Gram-negative bacteria. The effect of Endotoxins is relatively weak in terms of induced in the host organism, except when they are produced in large quantities and expressed massively into the host organism. Endotoxins may be released from bacteria as they grow in large numbers within the host organism; or from bacteria cells that are lysed as a result of effective host defence mechanisms, or by the activities of certain antibiotics which are introduced into the host cell to ward off or eliminate the invading pathogenic bacteria. The damaging action of Endotoxins to the host organism can be generally felt, or the toxin can be effective when it is present within the cell walls of living bacteria. However, the greatest effect of Endotoxins is usually noticeable and acutely felt by the host organism, when bacteria are killed or lysed and their products released into the systemic circulation of the host organism (Mansfield). The ability to produce toxins is generally specific to a particular bacterial species that causes the disease associated with the toxin. For example, only Clostridium tetani produces tetanus toxin, which can kill an adult human upon their coming in contact with only a tiny amount (microgram) of the toxin. Corynebacterium diphtheriae produces the diphtheria toxin, which is an enzyme that blocks protein synthesis within the host which the bacteria pathogen has been introduced through invasion of the host. Usually, virulent strains of the bacteria produce the toxin while non-virulent strains do not produce the toxin. On this basis, production of toxin is considered to be the major determinant of virulence. For example, tetanus is produced by virulent strains of Clostridium tetani while diphtheria in humans is produced by the virulent strains of Corynebacterium diphtheriae. At one time, it was thought that production of Exotoxins was limited mainly to Gram-positive bacteria; however, it is now clear that both Gram-positive and Gram-negative bacteria produce soluble protein toxins. (Atlas, 1994, p. 482) Classification of bacterial toxins based on the mode of action: There are many bacterial toxins produced by well-established or newly emergent pathogenic microbes. These toxins, which affect eukaryotic cells by a variety of means, include Staphylococcus aureus -toxin, Shiga toxin, cytotoxic necrotizing factor type 1, Escherichia coli heat-stable toxin, botulinum and tetanus neurotoxins, and S. aureus toxic-shock syndrome toxin. A variety of bacterial toxins listed above can be categorized according to their different modes of action These are: 1. Damaging of host cell membranes, such as, Staphyloccocus aureus-toxin which affects the host plasma membrane. It can also cause abscesses in the host organism. 2. Inhibiting protein-synthesis, such as, Corynebacterium diphtheria toxin, which is the main cause of Diphtheria. 3. Activating second messenger pathways, for example, Clostridium botulinum C2 toxin which can cause Botulism. Also there is Vibrio cholera toxin which causes cholera. 4. Inhibiting the release of neurotransmitters. 5. Activating the host immune response, such as the aureus enterotoxins, which cause food poisoning in the host organism. Bacterial Protein Toxins Bacterial protein toxins are the most powerful human poisons known and retain high activity at very high dilutions. Fig. 1: Diagrammatic representation that Bacterial protein toxins include different types of activities that influence particular cellular functions. It is also shown the mechanism of Many bacterial protein toxins on how they exert their toxicity by modifying important functions of the host cells. The relevant physiological functions of the cells can be determined by dissecting the actions of the bacterial toxins. (biken.osaka-u.ac.jp) Description of the Mode of Action in some Bacterial Toxins: 1- Many species of Clostridium are biochemically active; what is more, many species are highly toxigenic. For example, the toxins that produced by the organisms of tetanus and botulism attack nervous pathway and are referred to as neurotoxins.The organisms associated with gas gangrene attack soft tissues by producing toxins and aggressins,and are referred to as histotoxic. (Greenwood, Slack, Peutherer, & Barer, p. 240-part3) 2- Staphylococcal enterotoxins and a group of related proteins made by Streptococci are known to be responsible for food poisoning and shock in man and animals. These proteins have the ability to bind to human major histocompatibility complex proteins. The complex ligand so formed has specificity for a particular part of T cell receptors, V beta, and by engaging V beta, can stimulate many T cells. It is possible that some or all of the pathological effects of these toxins are caused by their ability to activate so many T cells in a short time. It is also likely that encounters with such toxins have caused mice, at least, to evolve mechanisms for varying their T cell V beta repertoires, such that they are less susceptible to attack by the toxins. (Marrack and Kappler, 1990) Figure 1. It can be seen from the diagram the mode of action of several bacterial toxins. A. Staphylococcus aureus -toxin can damage cellular membranes. That action occurs after binding and oligomerization. For example, the stem of the mushroom-shaped -toxin heptamer inserts into the target cell and disrupts membrane permeability as depicted by the influx and efflux of ions represented by red and green circles. B. Shiga toxins (Stx) can cause inhibition of protein synthesis. Holotoxin, which consists of an enzymatically active (A) subunit and five binding (B) subunits, enters cells through the globotriasylceramide (Gb3) receptor. The N-glycosidase activity of the A subunit then cleaves an adenosine residue from 28S ribosomal RNA, which halts protein synthesis. C. Examples of bacterial toxins that activate Secondary Messenger Pathways. Binding of the heat-stable enterotoxins (ST) to a guanylate cyclase receptor results in an increase in cyclic GMP (cGMP) that adversely effects electrolyte flux. By ADP-ribosylation or glucosylation respectively, the C3 exoenzyme (C3) of Clostridium botulinum and the Clostridium difficile toxins A and B (CdA & CdB) inactivate the small Rho GTP-binding proteins. Cytotoxic necrotizing factor (CNF) of E. coli and the dermonecrotic toxin (DNT) of Bordetella species activate Rho by deamidation (www.cdc.gov/ncidod/EID/vol5no2/schmittG.htm‎) Examples of Bacterial Toxins: Botulism Toxin: Inhibits acetylcholine release from motor nerve endings and kills the nerve cells. As will be discussed in the section on "#Food Borne Diseases", this is the most deadly toxin known. This is an exception to the "infection rule", since C. botulinum does not have to infect for the toxin to kill (however, it can infect grow and produce lethal toxin doses in babies). Toxin production only occurs if the bacterium is infected with a certain bacteriophage (different from the diphtheria toxin). Botulinum neurotoxin: BoNTs) are the most potent natural toxins known. The family of BoNTs comprises seven antigenically distinct serotypes (A to G) that are produced by various toxigenic strains of spore-forming anaerobic Clostridium botulinum. They act as metalloproteinases that enter peripheral cholinergic nerve terminals and cleave proteins that are crucial components of the neuroexocytosis apparatus, causing a persistent but reversible inhibition of neurotransmitter release resulting in flaccid muscle paralysis. They are the causative agent of the deadly food poisoning disease, botulism, and could pose a major biological warfare threat due to their extreme toxicity and ease of production.(wikipedia.org). Staphylococcal toxins: Immune evasion proteins from Staphylococcus aureus have a significant conservation of protein structures and a range of activities that are all directed at the two key elements of host immunity, complement and neutrophils. These secreted virulence factors assist the bacterium to survive the immune response. Diphtheria toxin: an enzyme that blocks protein synthesis in many cells. The bacterium producing this potent toxin grows mainly in the throat. Toxin production only occurs if the bacterium is infected with a certain bacteriophage. Tetanus toxin: Blocks the function of certain nerve cells which leads to spastic paralysis in the host. The bacterium that produces this toxin is anaerobic & usually grows locally in a puncture wound, such as that from a nail or rose thorn, yet it readily kills full grown horses or humans (Atlas, 1994 pp.481, 482) Conclusion In this paper, we have discoursed pathogenesis of bacteria. The Virulence factors which are produced by pathogenic bacteria when they invade host cells and cause pathogenesis and disease in their host organism. We also discussed the classification of bacteria toxins according to two major classifications: Classification of bacterial toxins based on the site of action and classification of bacterial toxins based on the mode of action. We discussed Bacterial Protein Toxins and gave descriptions of the mode of action in some of these bacterial toxins. Examples were given of bacterial toxins and the types of diseases which they cause in the host organisms into which they are expressed. Finally, bacterial pathogenesis and the consequent infectious process within the host organism were outlined. The five stages of the infectious process within the host organism after the pathogenic bacteria have successfully invaded its cells, tissues and organs were outlined. These stages begin with entry into the host cell with avoidance of host primary defences, then adhesion of the bacteria to host cell; which is followed by propagation of the pathogenic organism and which finally terminate at damage to host cells by bacterial toxins or an inflammatory response to the host and evasion of host secondary defences. References: 1. Atlas, Ronald M. (Ed) Principles of Microbiology, 1994 pp.481, 482 Greenwood, David; Slack, Richard; Peutherer, John; Barer, Mike. Medical Microbiology, 17th ed. 2007 Harvey, R.A., Champe, P.C., Fisher, B.D.: Lippincott’s Illustrated Reviews Microbiology, 2nd edition, pp, 11, 12, & 13). http://en.wikipedia.org/wiki/Virulence_factor Internet Sources: www.biken.osaka-u.ac.jp/act/images/horiguchiB.png www.cdc.gov/ncidod/EID/vol5no2/schmittG.htm Marrack, P. Kappler, J. Science, 1990 - sciencemag.org www.microbiologybytes.com/iandi/5.html www.news-medical.net/news/2007/08/24/29107.aspx http://www.umdnj.edu/research/publications/fall08/index.htm www.slic2.wsu.edu:82/.../pages/Chap13.html http://en.wikipedia.org/wiki/Microbial_toxins#cite_note-Langley-7 Read More

4. Bacterial toxins: Having entered into the cell matrix of the host organism, some bacteria pathogens cause disease by producing toxins which are poisonous to the host organism. Toxins are products of a pathogen that can destroy, or damage or deactivate one or more essential components of the host, thus allowing the pathogen to survive and increase within the infectious site. In fact, there are more than two hundred and twenty (220) known toxins produced by bacterial organisms. They can be classified into two main groups.

These are Exotoxins and Endotoxins. According to Harvey et al: “Microbial pathogenicity refers to the disease-causing as a result of microorganism’s activities… Bacterial toxins are considered as the most important part in the development of bacterial infections in a host organism. In other words a major group of virulence factors are bacterial toxins (Harvey, Champe, & Fisher). Production of Disease (Toxin-induced damage) Also, according to Harvey, et al, Toxigenesis, or the ability to produce toxins, is an underlying mechanism by which many bacterial pathogens produce disease in their host organisms.

It is well known that bacteria have developed a number of different techniques in which they can cause diseases; once they have succeeded in entering the body of their host organism. Thus, pathogenicity in bacteria may be said to be associated with unique structural components of the cells of the particular pathogenic bacteria. The unique structural components of pathogenic bacteria include capsules, some of which are: pili, lipopolysaccharides; or they may be active secretion of substances such as toxins, which may cause damage to local tissues in addition to damage to distant tissues within the same host organism; or may even protect the bacteria against defences put up by the host organism in its attempt to ward off the invading pathogenic bacteria.

Toxic substances produced by bacteria may be transported by the vascular or lymphatic system of the host organism, and cause cytotoxic effects at tissue sites within the host organism which are far removed from the original point of invasion or growth of the pathogenic bacteria. (Harvey, Champe, & Fisher) Classification of bacterial toxins based on the site of action: 1. Exotoxins Exotoxins include a huge number of proteins, which are often enzymes that are concealed from the host cell and which are mostly, but not exclusively, produced by gram positive bacteria inside the cells being invaded and which do their damage (as with Endotoxins) upon being released from the cell of the pathogenic bacteria into the tissues of the host organism.

It is well known that many Exotoxins have generalizable targets or sites of action, on the basis of which they are classifiable into three main categories. These three categories are: Cytotoxins, enterotoxins and neurotoxins. (microbiologybytes.com) According to Harvey et al: “These groups of toxins include some of the most poisonous sub-stances known. Exotoxins proteins have two types of polypeptide components; one is responsible for binding the protein to the host cell and the other one produce a toxic effect” (Harvey, pp. 12, 13). a.

A neurotoxin is a kind of bacterial toxin that acts specifically on nerve cells (neurons), of the host organism into which the pathogenic bacteria has invaded; usually by interacting with membrane proteins of the host organism such as channels. For example, Botulin which is produced by Clostridium botulinum causing botulism, and the other neurotoxin Tetanospasmin, which when produced by Clostridium tetani causes the pathologic condition in the host organism, called tetanus. (Atlas, 1994, pp. 481,482) b.

In case of Cytotoxins, they work to destroy host cells into which the invading bacteria have successfully penetrated. An example of this class of toxins is the alpha-toxin, which is produced by Clostridium perfringens. c. The class of toxin called Enterotoxins, are specially affect the cell lining the gastrointestinal tract in humans.

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