Types of toxins
- 1. Pt. Ravishankar Shukla University S.o.s in Biotechnology Topic :- Types of Toxins Guided By :- Dr. K K Shukla Submitted By :- P. Sujata Msc I sem
- 2. Pathogens Pathogenicity and Virulence Infection Virulence Adherence Damage of host cell Bacterial toxins Types of toxins Exotoxins o Cytolytic toxin o AB toxin o Superantigen toxin Endotoxins Natural Host Resistance
- 3. A host is an organism that harbors a pathogen, another organism that lives on or in the host and causes disease. The outcome of a host–pathogen relationship depends on pathogenicity, the ability of a pathogen to inflict damage on the host. Pathogenicity differs considerably among potential pathogens, as does the resistance or susceptibility of the host to the pathogen. An opportunistic pathogen causes disease only in the absence of normal host resistance.
- 4. PATHOGENICITY AND VIRULENCE Pathogenicity varies markedly for individual pathogens. The quantitative measure of pathogenicity is called virulence, the relative ability of a pathogen to cause disease. Virulence can be expressed quantitatively as the cell number that elicits disease in a host within a given time period. The host–pathogen interaction is a dynamic relationship between the two organisms, influenced by changing conditions in the pathogen, the host, and the environment.
- 5. Infection Infection refers to any situation in which a microorganism is established and growing in a host, whether or not the host is harmed. Disease is damage or injury to the host that impairs host function. Infection is not synonymous with disease because growth of a microorganism on a host does not always cause host damage. Thus, species of the normal microflora have infected the host, but seldom cause
- 6. Virulence Virulence is a pathogen's or microbe's ability to infect or damage a host. virulence refers to the degree of damage caused by a microbe to its host. The various traits or factors that allow microorganisms to cause disease. These include: Adhesion organelles Toxin production Evasion of host immune response Resistance to antibiotics Ability to invade host tissues
- 7. A pathogen must usually gain access to host tissues and multiply to cause disease. In most cases, this requires that the organisms penetrate the skin or mucous membranes, surfaces that are normally microbial barriers. Most microbial infections begin at breaks or wounds in the skin or on the mucous membranes of the respiratory, digestive, or genitourinary tract. Bacteria or viruses able to initiate infection often adhere to epithelial cells through specific interactions between molecules on the pathogen and molecules on the host cell In addition, pathogens often adhere to each other, forming biofilms.
- 8. Most pathogens selectively adhere to particular types of cells localized in a particular region of the body. For example, Neisseria gonorrhoeae, the pathogen that causes the sexually transmitted disease gonorrhea, adheres to mucosal epithelial cells in the genitourinary tract, eye, rectum, and throat. Streptococcus pyogenes utilizes two cell-wall- associated molecules, the M protein and lipoteichoic acid, to form microfibrils that facilitate attachment to host cells M protein is also responsible for resistance to phagocytosis by neutrophils, cells important in antibacterial resistance.
- 9. Influenza virus occurs in nature as an avian pathogen, targeting the lung mucosal cells. A polymer coat consisting of a dense, well- defined polymer layer surrounding the cell is called a capsule. Both slime layers and capsules are important for adherence to other bacteria as well as to host tissues.
- 10. Fimbriae and pili are bacterial cell surface protein structures that may function in the attachment process. For instance, the pili of Neisseria gonorrhoeae play a key role in attachment to the urogenital epithelium, and fimbriated strains of Escherichia coli are more frequent causes of urinary tract infections than strains lacking fimbriae. Flagella can also increase adherence to host cells.
- 12. Microbial toxins are toxins produced by micro- organisms, including bacteria and fungi. Microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system.
- 13. Types of toxins
- 14. Exotoxins are toxic proteins released from the pathogen cell as it grows.These toxins travel from a site of infection and cause damage at distant sites. Exotoxins fall into three categories: the cytolytic toxins, the AB toxins, and the superantigen toxins. 1.The cytolytic toxins work by degrading cytoplasmic membrane integrity, causing lysis. 2.The AB toxins consist of two subunits, A and B.The B component binds to a host cell surface receptor, facilitating the transfer of the A subunit across the targeted cytoplasmic membrane, where it damages the cell. 3.The superantigens work by stimulating large numbers of immune cells, resulting in extensive inflammation and tissue damage. A subset of the exotoxins are the enterotoxins, exotoxins whose activity affects the small intestine, generally causing secretion of fluid into the intestinal lumen resulting in vomiting and diarrhea.
- 16. Cytolytic Toxins Cytolytic toxins are secreted, soluble, extracellular proteins produced by a variety of pathogens. Cytolytic toxins damage the host cytoplasmic membrane, causing cell lysis and death. Because the activity of these toxins is most easily observed with assays involving the lysis of red blood cells (erythrocytes), the toxins are often called hemolysins However, they also lyse cells other than erythrocytes. Some hemolysins attack the phospholipid of the host cytoplasmic membrane. Because the phospholipid lecithin (phosphatidylcholine) is often used as a substrate, these enzymes are called lecithinases or phospholipases. An example is the α-toxin of Clostridium perfringens, a lecithinase that dissolves membrane lipids, resulting in cell lysis Because the cytoplasmic membranes of all organisms contain phospholipids, phospholipases sometimes destroy bacterial as well as animal cytoplasmic membranes.
- 17. Cytolytic Toxin :-Example Staphylococcal α-toxin kills nucleated cells and lyses erythrocytes. Toxin subunits first bind to the phospholipid bilayer. The subunits then oligomerize into nonlytic heptamers, now associated with the membrane. Following oligomerization, each heptamer undergoes conformational changes to produce a membrane-spanning pore, releasing the cell contents and allowing influx of extracellular material, disrupting cell function and causing cell death.
- 19. AB TOXINS AB Toxins Several pathogens produce AB exotoxins that inhibit protein synthesis. The diphtheria toxin produced by Corynebacterium diphtheriae is an AB toxin and an important virulence factor. Rats and mice are relatively resistant to diphtheria toxin, but human, rabbit, guinea pig, and bird cells are very susceptible, with only a single toxin molecule required to kill each cell. Diphtheria toxin is secreted by C. diphtheriae as a single polypeptide. Fragment B specifically binds to a host cell receptor present on many eukaryotic cells, the heparin-binding epidermal growth factor . After binding, proteolytic cleavage between fragment A and B allows entry of fragment A into the host cytoplasm. Here fragment A disrupts protein synthesis by blocking transfer of an amino acid from a tRNA to the growing polypeptide chain The toxin specifically inactivates elongation factor 2 (EF-2), a protein involved in growth of the polypeptide chain, by catalyzing the attachment of adenosine diphosphate (ADP) ribose from NAD1. Following ADP-ribosylation, the activity of the modified EF-2 decreases dramatically and protein synthesis stops. Diphtheria toxin is encoded by the toxgene in a lysogenic bacteriophage called phage β. Toxigenic, pathogenic strains of C. diphtheriaeare infected with phage βand encode the toxin. Nontoxigenic, nonpathogenic strains of C. diphtheriaecan be converted to pathogenic strains by infection with phage β, a process called phage conversion.
- 22. Tetanus and Botulinum Toxins Clostridium tetani and Clostridium botulinum are endospore forming bacteria commonly found in soil. These organisms occasionally cause disease in animals through potent AB exotoxins that are neurotoxins—they affect nervous tissue. All pathogenic effects are due to neurotoxicity. C. botulinum sometimes grows directly in the body, causing infant or wound botulism, and also grows and produces toxin in improperly preserved foods . Death from botulism is usually from respiratory failure due to flaccid muscle paralysis. C. tetani grows in the body in deep wounds that become anoxic, such as punctures. Although C. tetani does not invade the body from the initial site of infection, the toxin can spread via the neural cells and cause spastic paralysis, the hallmark of tetanus, often leading to death .
- 23. Botulinum toxins, the most potent biological toxins known, are seven related AB toxins. One milligram of botulinum toxin is enough to kill more than 1 million guinea pigs. The major toxin is a protein that forms complexes with nontoxic botulinum proteins to yield a bioactive protein complex. The complex then binds to presynaptic membranes on the termini of the stimulatory motor neurons at the neuromuscular junction, blocking the release of acetylcholine. Normal transmission of a nerve impulse to a muscle cell requires acetylcholine interaction with a muscle receptor; botulinum toxin prevents the poisoned muscle from receiving the excitatory acetylcholine signal . This prevents muscle contraction and leads to flaccid paralysis and death by suffocation, the outcome of botulism.
- 25. Tetanus toxin Tetanus toxin is also an AB protein neurotoxin. On contact with the central nervous system, this toxin is transported through the motor neurons to the spinal cord, where it binds specifically to ganglioside lipids at the termini of the inhibitory interneurons. The inhibitory interneurons normally work by releasing an inhibitory neurotransmitter, typically the amino acid glycine, which binds to receptors on the motor neurons. Glycine from the inhibitory interneurons then stops the release of acetylcholine by the motor neurons and inhibits muscle contraction, allowing relaxation of the muscle fibers. However, if tetanus toxin blocks glycine release, the motor neurons cannot be inhibited, resulting in tetanus, continual release of acetylcholine, and uncontrolled contraction of the poisoned muscles The outcome is a spastic, twitching paralysis, and affected muscles are constantly contracted. If the muscles of the mouth are involved, the prolonged contractions restrict the mouth’s movement, resulting in a condition called lockjaw(trismus). If respiratory muscles are involved, prolonged contraction may result in death due to asphyxiation.
- 27. Cholera Toxin- Enterotoxin Cholera toxin, an enterotoxin produced by V. cholerae, causes cholera . Cholera is characterized by massive fluid loss from the intestines, resulting in severe diarrhea, life threatening dehydration, and electrolyte depletion . The disease starts by ingestion of V. cholerae in contaminated food or water. The organism travels to the intestine, where it colonizes and secretes the cholera AB toxin. In the gut, the B subunit binds specifically to GM1 ganglioside, a complex glycolipid found in the cytoplasmic membrane of intestinal epithelial cells. The B subunit targets the toxin specifically to the intestinal epithelium but has no role in alteration of membrane permeability; the toxic action is a function of the A chain, which crosses the cytoplasmic membrane and activates adenylate cyclase, the enzyme that converts ATP to cyclic adenosine monophosphate (cAMP). The cAMP molecule is a cyclic nucleotide that mediates many different regulatory systems in cells, including ion balance. The increased cAMP levels induced by the cholera enterotoxin induce secretion of chloride and bicarbonate ions from the epithelial cells into the intestinal lumen. This change in ion concentrations leads to the secretion of large amounts of water into the intestinal lumen. In acute cholera, the rate of water loss into the small intestine is greater than the possible reabsorption of water by the large intestine, resulting in a large net fluid loss. Cholera treatment is by oral fluid replacement with solutions containing electrolytes and other solutes to offset the dehydration coupled ion imbalance. Expression of cholera enterotoxin genes ctxA and ctxB is controlled by toxR. The toxR gene product is a transmembrane protein that controls cholera A and B chain production as well as other virulence factors, such as the outer membrane proteins and pili required for successful attachment and colonization of V.cholerae in the small intestine.
- 29. superantigens Exotoxins called superantigens act by stimulating as many as 30% of host T cells to over express and release massive amounts of cytokines from other host immune cells in the absence of a specific antigen . The excessive concentration of cytokines causes multiple host organs to fail, giving the pathogen time to disseminate. By triggering this “cytokine storm,” superantigens cause life-threatening disease; fever, fluid loss, and low blood pressure result in shock and death.
- 31. The lipopolysaccharide (LPS) in the outer membrane of Gramnegative bacteria is toxic to humans. LPS is called an endotoxin because it is bound to the bacterium and is released when the microorganism lyses, although some may also be released during cell division. The toxic component of LPS is the lipid portion, called lipid A. Lipid A is not a single macromolecular structure; rather, it is a complex array of lipid residues. Lipid A is heat stable and toxic in nano gram amounts but only weakly immunogenic. Typical Gram negative cell walls include additional layers besides peptidoglycan .
- 32. The lipid A of various Gram-negative bacteria produces similar systemic effects regardless of the microbe from which it is derived. These include fever (i.e., endotoxin is pyrogenic), shock, blood coagulation, weakness, diarrhea, inflammation, intestinal hemorrhage, and fibrinolysis (enzymatic breakdown of fibrin, the major protein component of blood clots) The main biological effect of lipid A is an indirect one, mediated by host molecules and systems, rather than by lipid A itself. For example, endotoxins initially activate a protein called the Hageman factor (blood clotting factor XII), which in turn results in unregulated blood clotting within capillaries (disseminated intravascular coagulation) and multi organ failure. Endotoxins also indirectly induce a fever in the host by causing macrophages to release endogenous pyrogens that reset the hypothalamic thermostat. One important endogenous pyrogen is the cytokine interleukin-1 (IL-1). Other cytokines released by macrophages such as the tumor necrosis factor, also produce fever. The net effect is often called septic shock and can also be induced by certain pathogenic fungi and Gram-positive bacteria.
- 35. NATURAL HOST RESISTANCE Physical and Chemical Barriers The structural integrity of tissue surfaces poses a barrier to penetration by microorganisms. In the skin and mucosal tissues, potential pathogens must first adhere to tissue surfaces and then grow at these sites before traveling elsewhere in the body. Resistance to colonization and invasion is due to the production of host defense substances and to various anatomical mechanisms. The skin is an effective barrier to the penetration of microorganisms. Sebaceous glands in the skin secrete fatty acids and lactic acid, lowering the acidity of the skin to pH 5 and inhibiting colonization of many pathogenic bacteria (blood and internal organs are about pH 7.4). Microorganisms inhaled through the nose or mouth are removed by ciliated epithelial cells on the mucosal surfaces of the nasopharynx and trachea. Potential pathogens ingested in food or water must survive the strong acidity in the stomach (pH 2) and then must compete with the abundant resident microflora present in the small and large intestines. Finally, the lumen of the kidney, the eye, the respiratory system, and the cervical mucosa are constantly bathed with secretions such as tears and mucus containing lysozyme, an enzyme that can digest the cell wall and kill bacteria
- 36. Reference Brock -Biology of Microorganisms 13th Edition Prescott’s - Microbiology 10th Edition
- 37. Thank you