Microbiology Lecture 8 - Pathogenesis and Toxigenicity Part 1

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Microbiology Lecture 8 - Pathogenesis and Toxigenicity Part 1
2013-10-19 20:07:39
Bio 474

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  1. What are toxins ?

    What are they composed of ?

    Can toxins be fatal ?
    Toxin: microbial poison; any substance that is toxic to a cell

    Toxins are proteins made by living organisms (and other organisms) that have a negative or toxic effect on the host

    Sometimes the effect of toxins can be fatal to the host
  2. What is Toxigenicity ?

    Can an organism be described as "Toxogenic" ?

    Can the DNA for Toxins be transferred on a plasmid?
    The capacity of microbes to make and secrete toxins.

    Microbes can be described as toxigenic.The organism carries genes for these toxic molecules on their chromosome

    Some toxins are plasmid-borne and can be shared between related species by horizontal/lateral transfer
  3. What is Toxinosis ?

    What is Intoxication ?

    What is Toxemia ?
    Toxinosis : disease caused by a toxin.Requires the pathogen to colonize, grow and produce toxins that are secreted.

    Intoxication: disease that results from ingestion of the (pre-formed) toxin does not require the pathogen

    Toxemia: the presence of toxins in the blood
  4. What is Toxicology ?

    What is a Toxoid ?

    What are Antitoxins ?
    Toxicology: the study of toxins, including structure, mechanism of action, regulation, etc.

    Toxoid: attenuated (weakened) toxin; used to as vaccines to stimulate a protective immune response

    Antitoxins: antibodies produced by the body (animal host) to neutralize toxins
  5. Can a Toxin cause cytolysis ?

    Do Toxins interfere with the metabolic process?

  6. What are these effects of Toxins ?

    • emetic - vomiting 
    • Neoplastic - tumor growth
  7. What are proenzymes ?
    Are produced as proenzymes within the microbe; this form is inactivy.The toxin is then activated once it leaves the cell via Enzymatic cleavage or phosphorylation
  8. How are bacterial toxins listed ?

    What are toxins called that are harmful to other bacteria  ?

    What are Bacteriocins called that are beneficial to humans ?

    What does the term antigenic mean ?
    Bacterial toxins harmful to humans are listed by the body system they target.

    If toxic to other bacteria, they are called bacteriocins.If these toxins are used in the treatment of human bacterial infections, they are called antibiotics

    Toxins are antigenic; stimulates the immune system
  9. What are toxins made by fungi called ?
  10. What is algal toxin called ?

    • Cyanobacteria: Bacteria
    • Dinoflagellates: Protozoa

    Are the cause of shellfish poisoning in humans
  11. What are endotoxins and exotoxins ?
    Exotoxins: toxins secreted by live bacteria

    Endotoxins: released when the bacteria dies
  12. Based on Definition 1: Based on the viability of the bacterial cell What are the function of endotoxins and exotoxins ?
    Exotoxins: toxins secreted by live bacteria

    Endotoxins: released when the bacteria dies
  13. Based on Definition 2: Based on the location of the toxins in relation to the bacterial cell , what are the function of endotoxins and exotoxins ?
    Exotoxins: toxins released into the surrounding area

    Endotoxins: are critically associated with the bacteria
  14. Based upon Definition 3: Based on the action of the toxin , what are the funtion of endotoxins and exotoxins ?
    Exotoxins: work on intracellular targets of the host cell

    Endotoxins: work at the surface of the host cell
  15. Are exotoxins made by both gram - and gram + bacteria ?

    Do all bacteria make exotoxins ?

    Where are exotoxins made?

    Are they enzymes ?


    In the cytoplasm - ribosomes

  16. Whic toxins are more potent , intracellular or extracellular ?
  17. How do conformations effect the way toxins leave and enter the cell ?

    Does conformation effect the function of the toxin ?
    Some toxins are exported across the plasma membrane into the host cell and then folded to the correct conformation.Active once the correct conformation is achieved.

    Some toxins are made and folded within the bacterial cell and are only exported if they have the correct conformation.
  18. Where do the following toxins act ?




    Neurotoxins: act on the nervous system

    Enterotoxins: act on the gastrointestinal tract (also known as the enteric system).Commonly associated with food poisoning

    • Nephrotoxins: damage the
    • kidneys

    Hepatotoxins: damage the liver
  19. What are some effect of neurotoxins ?
    Can result in flaccid (limp) or rigid paralysis .E.g. botulinum toxin made by Clostridium botulinum; etiological agent for botulism, a severe form of food poisoning

    Can cause rigid paralysisE.g. tetanus toxin made by Clostridium tetani; etiological agent for tetanus (or lockjaw)
  20. What are some effects of enterotoxins ?
    Are exotoxins that specifically target the intestinal mucosa

    • Affect cAMP levels
    • Result in increase elimination of water from intestinal cells

    Cause vomiting and diarrhea
  21. What are cytotoxins ?
    because the action of the toxin is within the cytoplasm

    The toxin is secreted directly into the cytosol in a contact-dependent manner

    Advantages -Efficient: poison enters only the target cell

    Selective: intracellular target is specific
  22. Do gram - or gram + cytoxins make a pore or inject it ?
    gram + make a pore 

    gram - inject it
  23. What is Type  III and Type IV toxin injection of gram negatve bacteria ?
    Molecular syringes that resemble flagella (Type III)

    Molecular syringes that resemble conjugative pili (Type IV)
  24. What are AB toxins ?

    What are the differences between the unit ?
    A Toxin enters without the aid of the bacteria

    B domain/subunit Binds to cell surface receptors of host Helps to translocate the A domain/subunit A domain/subunit.

    Is transferred across the plasma membrane into the host cellEnters the cytoplasm and enzymatically acts on host targets
  25. What is Diptheria Toxin ?
    -Diphtheria toxin isAn AB toxin Produced by Corynebacterium diphtheriae

    -The A sub-unit inhibits protein synthesis by blocking the transfer of an amino acid from the tRNA to the polypeptide.Specifically inactivates elongation factor 2 (EF-2)

    -Diphtheria is a childhood disease of the respiratory system
  26. What is Botulin ?
    Botulin (also called Botulinum toxin)

    Produced by Clostridium botulinum.Is a group of seven related A-B toxins; 1A + 1B

    Are the most potent biological toxins known

    Binds to the pre-synaptic membranes of stimulatory motor neurons found at the neuromuscular junction.Blocks the release of acetylcholine (neurotransmitter).This prevents the muscle from receiving an excitatory signal.No muscle contraction
  27. What is Tetanospasmin (also called tetanus toxin ) ?
    • Produced by Clostridium tetani
    • An A-B toxin Targets the motor neuronsIs transported to the spinal column and binds to ganglioside lipids of inhibitory neurons

    Inhibitory neurons produce glycine which stops the release of acetylcholine, which causes muscles to contract

    Tetanospasmin blocks the release of glycine, resulting in continuous contraction of muscles.
  28. What is Cholera Toxin (also called choleragen) ?
    Cholera toxin is called choleragen

    Produced by Vibrio cholerae Is an A-B toxin: 1A + 5B Binds to the ganglioside GM1 of intestinal epithelial cells

    Activates the enzyme, adenyl cyclase which causes increased production of cAMP

    cAMP prevents the movement of Na+ in cells and the net movement of Cl- out of cells

    The change in ion concentration results in the secretion of large amounts of water from the small intestine

    Water reabsorption by the large intestine is slower than water loss

    Patients suffer severe dehydration
  29. How do Cytolytic Toxins work ?
    Work by enzymatically attacking the cell causing cell lysis.The action of these toxins are most easily observed with erythrocytes, hence they are often called hemolysins

    They also work on cells other than erythrocytesAction is observed by streaking the organism on (sheep’s) blood agar plates
  30. Are these all types of Cytolytic Toxins?

    A. Hemolysins
    B. Streptolysin
    C. Lecithinases or phospholipases
    D. Leukocidins
  31. What are Hemolysins ?
    Hemolysins they are Produced by: staphylococci, streptococci, clostridia, Escherichia

    Hemolysis: Lyses red blood cells (erythrocytes)

    • Results in anemia
    • Purpose:Allows pathogen greater access to iron

    Action: Enzyme causes pore-formation in the plasma membrane,Death is by necrosis (lysis of the cell where the cellular contents spill out and damage neighboring cells)Also destroys leucocytes (white blood cells
  32. What are the three types of hemolysis ?

    Alpha Hemolysis 
    Beta Hemolysis
    Gamma Hemolysis
    Alpha hemolysis: the partial destruction of erythrocytes (RBCs)

    Beta hemolysis: the complete destruction of erythrocytes (RBCs)

    Gamma hemolysis: no hemolysis
  33. What to streptococci Hemolysins work on ?
    Hemolysins produced by the streptococci Does not work on the phospholipids of the cell membrane. Instead, works on sterols.Similar effect to hemolysins in staphylococci.

    Example: streptolysin A; streptolysin O
  34. What do Lecithinases/Phospholipases do ?
    Lecithin is a phospholipid that protects cells from oxidative stress

    • Action: Enzymes that hydrolyze membrane phospholipids (e.g. lecithin)
    • Purpose: disrupt plasma membrane Damages the cell resulting in cell death and release of cellular contents

    e.g. alpha toxin of Clostridium perfringens
  35. What are leukocidins ?
    Produced by: staphylococci, streptococci, and some bacilli

    Result:Destroy host white blood cells (leukocytes)causes the disintegration of macrophages and neutrophils

    Purpose:Prevents phagocytosisReduces the immune response
  36. How do Leukocidins function ?
    Action:Enzyme attaches to the plasma membrane of leukocytes

    Causes pores to form Results in the degranulation of lysosomes within leukocytestriggers the release of lysosomal enzymes into the cytoplasm
  37. What is Leukostatin ?
    Leukostatin Produced by several species of bacteria

    Action: Interferes with the ability of phagocytes to phagocytize cellsPurpose: anti-phagocytic
  38. What is Collagenase ?
    Collagenase Produced by: clostridia

    • Action: hydrolyzes collagen Collagen: the fibrous protein constituent of bone, cartilage, tendon, and other connective tissue.
    • Forms the framework for connective tissuesPurpose: Allows for deeper penetration into tissue
  39. What is Hyaluronidase ?
    Produced by: staphylococci, streptococci, clostridia•

    Also called spreading factor•Action: Hydrolyzes hyaluronic acid (HA)•HA is a glue-like substance (mucopolysaccharide) that helps to hold cells of tissues together; sometimes referred to as “tissue cement”.•

    Purpose: tissue penetration•Allows bacteria to pass between epithelial cells and move deeper into tissues
  40. What is Elastase ?
    ElastaseProduced by several bacterial species (next slide)

    Action: Breaks down elastin and lamininElastin is an elastic protein found in connective tissue, along with collagen.

    It allows many tissues in the body to resume their shape after stretching or contracting.Laminin is a major protein of the basal lamina, part of the basement membrane of tissues and organs

    Purpose: Allows for deeper penetration into tissue.
  41. What are proteases ?
    Proteases Proteases are also referred to as peptidases or proteinases

    Purpose: to destroy or cleave proteins

    Several types of microbial proteases are important in establishing an infection
  42. What is the purpose of immunoglobulin Protease ?
    Immunoglobulin a Protease Produced by: Streptococcus pneumoniae IgA plays an important role in protecting the host against respiratory pathogens

    Action:Cleaves IgA into the two parts—the Fab portion and the Fc portionPurposeInactivates IgA; decreases the immune response
  43. What is the purpose of Cysteine protease ?
    Cysteine proteaseProduced by Streptococcus pyogenes

    • Action:Degrades proteins
    • Purpose: destroys antibodies decreases the immune response, especially opsonization and antigen presentation (specific immunity)

    Inactivates complement (innate immunity)
  44. What is Coagulase ?
    Coagulase•Produced by: Staphylococcus aureus and Yersenia pestis•Boils and abscesses are associated pathologies.•Action: Catalyzes blood clotting;•coagulates fibrinogen present in plasma;•accelerates coagulation rates during an infection•Fibrinogen is a glycoprotein produced by the liver and present in blood plasma; is essential for blood clotting.•Purpose:•Facilitates resistance to phagocytosis•Protects the pathogen from phagocytic leukocytes such as macrophages and neutrophils
  45. What are Kinases ?
    KinasesAlso called fibrolysinsProduced by:staphylococci (staphylokinase)streptococci (streptokinase)Action: digests blood clots; breaks down fibrinPurpose: Prevents isolation of infectionWhen coagulation occurs, pathogens are trapped in a local area in the blood stream and cannot disseminateDissolving blood clots allows for greater tissue penetration and the spread to other areas of the body
  46. What are Lipases ?
    Lipases Present in staphylococciAction: digests lipids

    Purpose: Helps bacteria to colonize oily skin
  47. What is nuclease ?
    NucleaseRefers to deoxyribonuclease(Dnase)Produced by: staphylococci, streptococciAction: cleaves DNAPurpose:Destroys leukocytes; anti-phagocyticLowers the viscosity of exudate, giving the pathogen greater latitude for spreadingExudate: fluid that has escaped out of tissues or blood vessels due to injury or inflammation
  48. What are Beta-Lactamases ?
    Beta-lactamasesPresent in many different species, especially staphylococci and streptococciAction: cleaves members of the penicillin drug familyPurpose: Confers resistance to beta-lactam antibioticsBeta-lactam drugs work on peptidoglycan, preventing cell wall synthesis, ultimately leading to cell deathAllows pathogen/infection to persist
  49. What is Mucinase ?
    MucinasePresent in Entamoeba histolytica (protozoa)Enzyme digests the protective coating on mucous membranesIs a virulence factor in amebic dysentery
  50. What is Keratinase ?
    KeratinaseDigests keratin, the principal component of skin and hairPresent in dermatophytesDermatophytes: fungal species that reside in the epidermal layer of the skin.Organisms cause superficial cutaneous infectione.g. ring worm (also called tinea)
  51. What are superantigens ?
    SuperantigensProteins that activate a large number of T-lymphocytes, without stimulation by specific antigensPresent in bacteria and virusesActivates T-cells with different antigen specificitiesEffect: T-cells release a large amount of cytokines, which may lead to organ failure and immunosuppression

    Examples:Staphylococcal enterotoxins (specifically SE-B)There are 24 different typesStaphylococcal toxic shock syndrome toxin, 1 and 2