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Pathogenesis41

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Pathogenesis41

  1. 1. GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Faculty: Dr. Alvin Fox
  2. 2. Key Words Pathogen Transmission Outbreak, Epidemic, Pandemic Adhesion Normal flora Penetration Infection Invasiveness/spread Infectious diseases Extra/intra cellular pathogen Compromised host Exotoxin Opportunistic infection Endotoxin - non-specific immunity Nosocomial Specific immunity Koch’s postulates Autoimmunity Bioterrorism
  3. 3. Pathogenicity <ul><li>virulence factors </li></ul><ul><li>number of initial organisms </li></ul><ul><li>immune status </li></ul>
  4. 4. Pathogens <ul><li>The “usual” rate </li></ul><ul><li>Oubreak - local </li></ul><ul><li>Epidemic - regional/national </li></ul><ul><li>Pandemic – widespread (international) </li></ul><ul><ul><li>infections “beyond the norm” </li></ul></ul>
  5. 5. Koch's postulates <ul><li>isolated </li></ul><ul><ul><li>diseased not healthy people </li></ul></ul><ul><li>growth </li></ul><ul><ul><li>pure culture </li></ul></ul><ul><li>induce disease </li></ul><ul><ul><li>susceptible animals </li></ul></ul><ul><li>re-isolated </li></ul><ul><ul><li>susceptible animals </li></ul></ul>
  6. 6. Opportunistic infections <ul><li>compromised people </li></ul><ul><ul><li>normal flora </li></ul></ul><ul><ul><li>environment </li></ul></ul>
  7. 7. Opportunists - normal flora <ul><ul><li>Skin </li></ul></ul><ul><ul><ul><li>Staphylococcus aureus , </li></ul></ul></ul><ul><ul><ul><li>S. epidermidis </li></ul></ul></ul><ul><ul><ul><li>Propionibacterium acnes </li></ul></ul></ul><ul><ul><li>Intestine </li></ul></ul><ul><ul><ul><li>Bacteroides </li></ul></ul></ul><ul><ul><ul><ul><li>high numbers </li></ul></ul></ul></ul><ul><ul><ul><li>Enterobacteriaceae </li></ul></ul></ul><ul><ul><ul><ul><li>low number </li></ul></ul></ul></ul>
  8. 8. Opportunists - environment <ul><li>air </li></ul><ul><li>water </li></ul><ul><li>soil </li></ul><ul><li>food </li></ul>
  9. 9. Opportunists in hospital <ul><li>nosocomial </li></ul>
  10. 10. Transmission <ul><li>airborne droplets </li></ul><ul><li>food </li></ul><ul><li>water </li></ul><ul><li>sexual contact </li></ul>
  11. 11. Host defenses <ul><li>Gut </li></ul><ul><ul><li>peristalsis </li></ul></ul><ul><ul><li>defecation </li></ul></ul><ul><li>respiratory tract </li></ul><ul><ul><li>ciliary action </li></ul></ul><ul><ul><li>coughing </li></ul></ul><ul><ul><li>sneezing </li></ul></ul><ul><li>urogenital tract </li></ul><ul><ul><li>urination </li></ul></ul>
  12. 12. Adhesion adhesin EPITHELIUM receptor BACTERIUM
  13. 13. S. pyogenes fibronectin F-protein lipoteichoic acid
  14. 14. E. coli Fimbriae Flagella
  15. 15. E. coli fimbriae mannose Type 1 <ul><li>galactose </li></ul><ul><ul><li>glycolipids </li></ul></ul><ul><ul><li>glycoproteins </li></ul></ul>P
  16. 16. Penetration and spread Vibrio cholerae Salmonella enteritidis Salmonella typhi Epithelium Gut lumen Blood stream
  17. 17. Connective tissue destrction <ul><li>Helps bacterial dissemination </li></ul><ul><ul><li>collagenase </li></ul></ul><ul><ul><li>hyaluronidase </li></ul></ul>
  18. 18. Extracellular pathogens <ul><li>resistant to extra-cellular killing </li></ul><ul><li>killed on phagocytosis </li></ul><ul><li>resist killing </li></ul><ul><ul><li>by avoiding internalization </li></ul></ul>
  19. 19. Protein A inhibits phagocytosis Protein A immunoglobulin Fc receptor BACTERIUM PHAGOCYTE
  20. 20. M protein inhibits phagocytosis M protein peptidoglycan Complement fibrinogen r r r
  21. 21. Intracellular parasite No fusion Lysozome Phagosome Fusion Enter cytoplasm Bacteria Macrophage or neutrophil
  22. 22. Killing of intracellular parasite <ul><li>Cell mediated immunity </li></ul>
  23. 23. Tissue Injury <ul><li>exotoxins </li></ul><ul><li>endotoxins and non-specific immunity </li></ul><ul><ul><ul><li>- no antigen </li></ul></ul></ul><ul><li>specific immunity </li></ul><ul><ul><ul><li>- antigen </li></ul></ul></ul>
  24. 24. Exotoxins <ul><li>proteins </li></ul><ul><li>usually enzymes </li></ul><ul><li>destroy cellular structures </li></ul><ul><li>destroy extracellular matrix </li></ul>
  25. 25. A-B toxins Active Binding A Cell surface B
  26. 26. <ul><li>Diphtheria toxin and Pseudomonas exotoxin A </li></ul><ul><ul><li>ADP-ribosylates elongation factor (EF2) </li></ul></ul><ul><ul><li>inhibits protein synthesis </li></ul></ul><ul><ul><li>kills cells, destroys tissues </li></ul></ul>
  27. 27. Cholera toxin and E. coli labile toxin <ul><li>ADP-ribosylation of regulator </li></ul><ul><li>adenylate cyclase activation </li></ul><ul><li>cyclic AMP </li></ul><ul><li>active ion and water secretion </li></ul><ul><li>diarrhea </li></ul>
  28. 28. <ul><li>Shiga toxin - shigellosis </li></ul><ul><li>Shiga-like toxin – entero hemorrhagic E. coli </li></ul><ul><li>lyses 28S rRNA in ribosome </li></ul><ul><li>death of epithelial cells </li></ul><ul><li>poor water absorption </li></ul><ul><li>diarrhea </li></ul>
  29. 29. <ul><li>Botulinum toxin </li></ul><ul><ul><li>inhibits acetylcholine release </li></ul></ul><ul><ul><li>inhibits nerve impulses </li></ul></ul><ul><ul><li>muscles inactive </li></ul></ul><ul><ul><li>flacid paralysis </li></ul></ul><ul><li>Tetanus toxin </li></ul><ul><ul><li>inhibits glycine release </li></ul></ul><ul><ul><li>inactivates inhibitory neurons </li></ul></ul><ul><ul><li>muscles over-active </li></ul></ul><ul><ul><li>rigid paralysis </li></ul></ul>
  30. 30. <ul><li>Clostridium perfringens </li></ul><ul><ul><li>collagenase </li></ul></ul><ul><li>Staphylococcus aureus </li></ul><ul><ul><li>- hyaluronidase </li></ul></ul>Exotoxins - extracellular matrix of connective tissue
  31. 31. <ul><ul><li>Proteases </li></ul></ul><ul><ul><li>Phospholipases </li></ul></ul><ul><ul><li>Detergent-like action </li></ul></ul>Membrane damaging exotoxins
  32. 32. <ul><li>destroys blood vessels </li></ul><ul><li>stops influx inflammatory cells </li></ul><ul><li>creates anaerobic environment </li></ul><ul><li>allows growth of this strict anaerobe. </li></ul>C. perfringens phospholipase
  33. 33. Exotoxins <ul><li>Antibodies (anti-toxins) neutralize </li></ul><ul><ul><li>vaccination </li></ul></ul>
  34. 34. Endotoxin <ul><li>Lipopolysaccharide </li></ul><ul><li>peptidoglycan -endotoxin-like action </li></ul><ul><li>cell envelope components </li></ul><ul><li>not proteins/enzymes </li></ul>
  35. 35. <ul><li>hypotension (tissue pooling of fluids) </li></ul><ul><li>disseminated intravascular coagulation </li></ul><ul><li>fever </li></ul><ul><li>lack of effective oxygenation </li></ul><ul><li>overall system failure </li></ul>Septic shock
  36. 36. Endotoxins <ul><li>non-specific inflammation </li></ul><ul><li>cytokine release </li></ul><ul><li>complement activation </li></ul><ul><li>B cell mitogens </li></ul><ul><li>polyclonal B cell activators </li></ul><ul><li>adjuvants </li></ul>
  37. 37. Specific immunity and immunopathology <ul><li>chronic infection </li></ul><ul><ul><ul><li>tuberculosis </li></ul></ul></ul><ul><ul><ul><li>leprosy </li></ul></ul></ul><ul><ul><ul><li>syphilis </li></ul></ul></ul><ul><li>persisting bacterial remnants </li></ul><ul><li>autoimmunity </li></ul>
  38. 38. <ul><li>help survival on external surfaces </li></ul><ul><ul><li>H. influenzae </li></ul></ul><ul><ul><li>S. pneumoniae </li></ul></ul><ul><ul><li>N. gonorrhoeae </li></ul></ul><ul><ul><li>N. meningitidis </li></ul></ul>IgA proteases
  39. 39. Bioterrorism <ul><li>air </li></ul><ul><ul><li>most common </li></ul></ul><ul><li>no previous exposure </li></ul><ul><ul><li>zoonoses </li></ul></ul><ul><li>manifest initially </li></ul><ul><ul><li>colds/flu-like </li></ul></ul><ul><ul><li>death </li></ul></ul><ul><li>recognition </li></ul><ul><ul><li>clinically (e.g. common source clusters) </li></ul></ul><ul><ul><li>clinical microbiology </li></ul></ul><ul><ul><li>biodetection (environment) </li></ul></ul><ul><ul><ul><li>future </li></ul></ul></ul>

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