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Lecture 7

Bella Paniagua Pathogenic Microbiology College English 52 cards

Cards in this deck (52)

  1. 1Bacterial Toxins- first VF to be identified and studied
    - relatively easy to isolate and purify
    - biochemical experimentation
    - often very specific for target molecules
    - provide effective vaccines
  2. 2Toxins are produced by a wide range of bacteria for a wide ride of purposes, usually involving ______________.killing or impairing other cells or organisms
  3. 3In many cases toxins have a clear benefit 1. 2. 3. Caveat1. Disrupt cytokine signaling
    2. Kill professional phagocytes
    3. Kill cells to release iron and nutrients
    -> it's not obvious is ALL cases how the toxin provides a benefit for the bacteri
  4. 4Botulinum Toxin - Abbreviation - Produced by ? - Problems come from?-BoNT or BOTOX
    - Clostridium botulinum
    - Problems come from eating the toxin produced in anaerobic food or clostridial spores
    - Bacteria do not colonize the intestinal tract well
    - Not well designed to be a pathogen
  5. 5Botulinum Toxin - In nature - Purpose?- C. botulinum normally lives in anaerobic non-circulating water (not a lot of nutrients)
    - Toxins kill visitors that then fall into the water to become food
    - Toxin can travel up the food chain
  6. 6Figuring out the "Why's" of Toxins isn't simple because....- sometimes you have to examine the environment niches the bacteria occupy
    - many toxins are associated with PAIs or other HGT elements
    -> not normal parts of the bacterial genome, lysogenic phages carry toxins
  7. 7Characteristics of Bacterial Toxins Definition of Toxin- Come in all shapes and sizes with even more different naming methods
    TOXIN: any type of VF, secreted or not, that is toxic to the human or animal host
  8. 8Naming can be based on...- tissue type they attack
    - just a simple letter
    - named in order of discovery
    - species or disease they are from
    - enzymatic activity
    - biochemical property
    - immune reactivity
  9. 9NAMING - Tissue Type Examples- cytotoxin: wide variety of cells
    - neurotoxin: nerve cells
    - hepatotoxin: liver cells
    - leukotoxin: leukocytes
    - cardiotoxin: heart cells
    - enterotoxin: intestinal cells
    - verotoxin: vero cells
  10. 10NAMING - Simple Letter Name ExampleExotoxin A
    - Pseudomonas aeruginosa
  11. 11NAMING - Discovery Orderalpha-epsilon toxins
    Clostridium perfringens
  12. 12NAMING - Species or Disease Examples-Cholera Toxin (CT), Cholera from Vibrio Cholerae
    -Shiga Toxin (ST), from Shigella
    - Diphtheria Toxin (DT), diphtheria, from C. diphtheriae
    - Tetanus Toxin (TeNT), tetanus, from C. tetani
    - Botulinum Toxin (BoNT), botulism, from C. botulinum
  13. 13NAMING - Enzymatic Activity ExamplesAdenylate cyclase
    - Bordetella pertussis, Whooping Cough
    Lecithinase
    - C. perfringens, Gangrene
  14. 14NAMING - Biochemical Property ExamplesHeat-labile Toxin (HLT)
    Heat-stabile Toxin (HST)
    -> both found in certain strains of E.coli
  15. 15NAMING - Immune Reactivity ExamplesBoNT's have seven serotypes (A-G)
    - Abs to one won't react to the other
    BoNT/A, BoNT/B, BoNT/C, etc.
  16. 16Toxins can have more than one name (Examples)- Shiga-like Toxin (SLT), Verotoxin
    -> same toxin from E.coli
    - alpha-toxin, Lecithinase
    -> same toxin from C. perfringens
    - Osteolytic toxin, Dermonecrotic toxin, Mitogenic Toxin, PMT
    -> same toxin from Pasturella multocida
  17. 17Why is a single name usually not enough to be specific?There are many different types of the same toxin (e.g. Verotoxins, alpha toxins)
    - To avoid confusion, the bacteria name is used
  18. 18Classifying Toxins- Exotoxin
    - Endotoxin
    - Exoenzymes/Effector Protein
  19. 19Exotoxina toxin that is excreted from the bacteria into the media
    - usually protein
    - "standard"
  20. 20Endotoxina toxin that is part of the bacterial surface and is released during cell lysis
    - usually lipid-like molecules
    - not secreted
  21. 21Exoenzymes/Effector Proteinstoxins that are injected directly into the host cell via secretion systems
  22. 22Classifying toxins by mechanism of action: Type I-IIIType I: binds to the target cell surface and works extracellularly (Superantigens)
    Type II: Act on eukaryotic cell membranes to destroy their integrity (phospholipases, pore-forming cytotoxins)
    Type III: activates or inactivated an intracellular target or signaling pathway (A-B type toxins)
  23. 23Different kinds of bacterial toxins- Nonprotein toxins
    -> endotoxins, mycolactones
    - Protein exotoxins (secreted)
    -> Type I-III
    - Exoenzymes/Effectors
  24. 24Endotoxins- integral bacterial membrane components
    -> LPS, LTA, phosphatidylglycerol
    - LPS toxicity is mediated by Lipid A
    - Septic Shock
    -> over activation of immune cells
  25. 25CAUTION when treating Endotoxins because...- for some Gram-, caution when treating systemic bacterial infections that contain endotoxins with antibiotics that destroy the cell wall, because all you're doing is released the endotoxin into the "environment"
  26. 26Jarisch-Herxheimer Reaction and Endotoxins- Treating syphillis with penicillin or tetracycline
    - lesions due to the bodies own inflammatory response
    -> 50% primary, 90% secondary syphillis
  27. 27Some pathogens purposefully release parts of their cell membrane to cause...toxic effects
    e.g. Bordetella pertussis, Whooping Cough
  28. 28Pertussis - Endotoxin Disease- Bordetella tracheal cytotoxin (TCT)
    - Arrests ciliary movement
    - Extrudes ciliated cells from the epithelium
    - Releases inflammatory cytokine IL-2
    - Coughing the only way to expel mucus, predisposes individual to 2ndary infections
  29. 29Nonprotein Toxins - Mycolactones- polyketide-derived, lipid-like molecules produced to enhance growth
    - Cytotoxic and immunosuppressive prevents inflammation and pain, promotes skin lesion growth
  30. 30Protein Toxin - Type I + exampleSuperantigens
    - over activate immune system
    - TSS: Toxic Shock Syndrome Toxin (TSST), Staph aureus was found to be colonizing the vagina and growing in a particular type of tampon
    - (TSLS): Strep pyogenes toxin production in preexisting skin infections
  31. 31Protein Toxin - Type IIMembrane-Disrupting Toxin
    - Pore-forming toxins: create channels or holes
    - Destabilizing toxins: destroy integrity of membranes
  32. 32Protein Toxin - Type II Example- alpha toxin of C. perfringens destroys lecithin in animal cell membrane and contributes to gangrene by destroying cells and tissue
  33. 33Protein Toxins - Type IIIA-B Toxins
    - A: toxic/enzymatic, active
    - B: part binds to the host cell moves A domain into the cell
    Binding: Translocation - movement of the A portion from the outside of cell to inside
  34. 34Protein Toxins - Type III Simple A-B toxins-Single polypeptide chain
    - Usually separated by proteolytic cleavage
    - e.g. Diphtheria
    - B domain binds to host receptor, endocytosis, translocation, release of A domain
  35. 35Protein Toxins - Type III Complex A-B ToxinsLarge multi-subunit complexes
    - A portion attached to multi-subunit B-portion
    - e.g. Cholera, Anthrax, Pertussis
  36. 36A domain mechanism of Toxicity- Many A parts of A-B toxins have the same enzymatic activity
    - ADP-ribosyltransferases: move ADP-ribosyl groups from NAD to host protein
  37. 37A-B Toxin ADP-Ribosyltransferases- The host protein affected, and therefore the results of the added group, depends on the toxin
  38. 38Not all A sub-units are ADP-Ribosyltransferases. Explain.- Shiga Toxin A subunit cleaves rRNA, Also shuts down protein synthesis
    - Botulinum Toxin A subunits are zinc-dependent metalloproteases that cleave neuron-specific proteins
    Cause paralysis
    - Anthrax has two A subunits
    Adenyl cyclase
    Zn-dependent protease
  39. 39Exoenzymes/Effectors- Proteins directly injected into the host cell
    - Toxic activities are similar to A-B domains, no need for B domains
    - Harmless unless they can be injected into the host cell
  40. 40Corynebacterium diphtheriae- Gram+ rod
    - non-spore forming
    - nonmotile
    - aerobic
    - pleiomorphic
  41. 41Diphtheria- Corynebacterium diphtheriae
    - Commonly vaccinated for where money and health-care is available
    - Normally a disease in children and can be fatal in untreated individuals
  42. 42Diphtheria Toxin (DT)- one of most well studied
    - first example where the entire disease could be explained by the action of one molecule
    - helped promote concept of virulence factors
  43. 43Diphtheria Pathogenesis - Colonization - Adherence - Invasion- Colonization: inhalation of aerosols, bacteria colonize the throat
    - Adherence: remain in place, mucosal epithelia
    - Invasion: begin secreting DT killing mucosal cells, lymph node swelling, formation of pseudomembrane
  44. 44Pseudomembrane- greyish layer that extends into the throat and sometimes into the lungs
    - composed of fibrin, bacteria, immune cells
  45. 45Diphtheria Disease Symptoms- Pseudomembrane adheres tightly to the underlying tissue, removing causes bleeding
    - sudden death can occur from suffocation
  46. 46Diphtheria Toxicity- DT is slowly released into the bloodstream
    - causes organ damage and eventual organ failure
    - Serious forms of the disease: heart damage, lung damage, skin lesions
  47. 47DT Production- DT is encoded on a group of bacteriophages (beta and w corynebacteriophages)
    - production enhanced in low iron conditions
  48. 48DT Production- DtxRDtxR: diphtheria toxin regulation - repressor protein that binds iron
    - HIGH: binds to iron, binds to the DT operator, prevents tx of the toxin
    - LOW: no iron to bind, no binding to operator, toxin tx ensues
  49. 49DT Production, why?- to increase iron supply?
    - increase spread from person to person?
    - phage using bacteria to spread?
  50. 50Mechanism of Diphtheria Toxin- Simple Type III A-B Toxin
    - B fragment made of 2 domains:
    R - binds to HB-EGF receptor
    T - translocation domain, inserts into the membrane at low pH
  51. 51Specifics of Diphtheria Toxin- R domain binds to HB-EGF
    - DT is endocytosed
    - Low pH causes protonation of acidic a.a.'s making them less hydrophilic
    - Changes the conformation of DT
    - T domain inserts into vesicle, creates a pore that translocates the A, bind reduced, releases A into cytoplasm
  52. 52—

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College Pathogenic Microbiology Flashcards on Lecture 7, created by Bella Paniagua on 27/10/2015.
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Bella Paniagua
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