Ch15 Tolli


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Ch15 Tolli

  1. 1. Chapter 15 Microbial Mechanisms of Pathogenicity
  2. 2. Microbial Mechanisms of Pathogenicity <ul><li>Pathogenicity The ability to cause disease </li></ul><ul><li>Virulence The extent of pathogenicity </li></ul>
  3. 3. <ul><li>Mucous membranes – resp. tract, GI tract, conjunctiva, urogenital </li></ul><ul><li>Skin – damaged skin, hair follicles, sebaceous gland/sweat gland ducts </li></ul><ul><li>Parenteral route – direct deposition into tissues – punctures, bites, lacerations, injections, splitting </li></ul>Portals of Entry
  4. 4. <ul><li>ID 50 : Infectious dose for 50% of the test population </li></ul><ul><ul><li>Number of particles required to cause disease </li></ul></ul><ul><li>LD 50 : Lethal dose (of a toxin) for 50% of the test population </li></ul><ul><ul><li>Potency of a toxin </li></ul></ul>Numbers of Invading Microbes
  5. 5. Bacillus anthracis 250,000-1,000,000 endospores Ingestion 10,000-20,000 endospores Inhalation 10-50 endospores Skin ID 50 Portal of entry
  6. 6. <ul><li>Adhesions/ligands bind to receptors on host cells </li></ul><ul><ul><li>Glycocalyx Streptococcus mutans </li></ul></ul><ul><ul><ul><li>Glucosyltransferase converts glucose to dextran (sticky) to form glycocalyx </li></ul></ul></ul><ul><ul><li>Fimbriae Escherichia coli </li></ul></ul><ul><ul><ul><li>Adhesins specific for cells in GI tract </li></ul></ul></ul><ul><ul><li>M protein Streptococcus pyogenes </li></ul></ul><ul><ul><ul><li>Cell wall component </li></ul></ul></ul><ul><ul><li>Opa protein Neisseria gonorrhoeae </li></ul></ul><ul><ul><ul><li>Outer membrane protein, in addition to fimbriae </li></ul></ul></ul><ul><ul><li>Tapered end Treponema pallidum </li></ul></ul>Adherence
  7. 7. <ul><ul><li>Coagulase S. aureus Coagulate blood </li></ul></ul><ul><ul><li>Kinases S. pyogenes, S. aureus Digest fibrin clots </li></ul></ul><ul><ul><li>Hyaluronidase Streptococci, Clostridia Hydrolyses hyaluronic acid (cell junction carbohydrates) </li></ul></ul><ul><ul><li>Collagenase Clostridia Hydrolyzes collagen </li></ul></ul><ul><ul><li>IgA proteases Nieisseria Destroy IgA antibodies </li></ul></ul><ul><ul><li>Siderophores Take iron from host iron- binding proteins </li></ul></ul><ul><ul><li>Antigenic variation Alter surface proteins to evade immune response </li></ul></ul>Enzymes
  8. 8. Penetration into the Host Cell Figure 15.2 Invasins – rearrange actin fibers associated with host cell membrane Salmonella, E. coli Causes membrane ‘ruffling” – result of cytoskeletal disruption Microbe sinks into ruffle and is Ingested by cell. Actin can be used as propulsion once inside host cell (s higella spp)
  9. 9. Toxins <ul><li>Toxin Substances that contribute to pathogenicity </li></ul><ul><li>Toxigenicity Ability to produce a toxin </li></ul><ul><li>Toxemia Presence of toxin the host's blood </li></ul><ul><li>Toxoid Inactivated toxin used in a vaccine </li></ul><ul><li>Antitoxin Antibodies against a specific toxin </li></ul>
  10. 10. Exotoxin – many are enzyme-like Small LD 50 Yes (good antigen) Neutralized by antitoxin No (mostly…except type 1) Fever? Protein Chemistry By-products of growing cell Metabolic product Mostly Gram + Source
  11. 11. <ul><li>A-B toxins or type III toxins </li></ul>Exotoxins Figure 15.5
  12. 12. <ul><li>Membrane-disrupting toxins or type II toxins </li></ul><ul><li>(example – S taph. aureus, Streptococci spp.) </li></ul><ul><ul><li>Lyse host’s cells by: </li></ul></ul><ul><ul><ul><li>Making protein channels in the plasma membrane (e.g., leukocidins, hemolysins) </li></ul></ul></ul><ul><ul><ul><li>Disrupting phospholipid bilayer </li></ul></ul></ul><ul><ul><ul><li>Also allow escape from phagosomes into cytoplasm </li></ul></ul></ul>Exotoxins
  13. 13. <ul><li>Superantigens or type I toxins </li></ul><ul><ul><li>Cause an intense immune response due to release of cytokines from T-lymphocytes </li></ul></ul><ul><ul><li>Fever, nausea, vomiting, diarrhea, shock, death </li></ul></ul>Exotoxins
  14. 14. Exotoxins Superantigen. Enterotoxin. • Staphylococcus aureus + A-B toxin. Enterotoxin • Vibrio cholerae A-B toxin. Neurotoxin • C. tetani + A-B toxin. Neurotoxin • Clostridium botulinum + Membrane-disrupting. Erythrogenic. • Streptococcus pyogenes + A-B toxin. Inhibits protein synthesis. • Corynebacterium diphtheriae Lysogenic conversion Exotoxin
  15. 15. Exotoxins Figure 15.4a
  16. 16. Endotoxin Figure 15.4b
  17. 17. Endotoxins Figure 15.6 (A cytokine) TNF – tumor necrosis factor – another cytokine secreted by phagocytes– damages capillaries
  18. 18. Endotoxins Relatively large LD 50 No (poor antigen) Neutralized by antitoxin Yes Fever? Lipid-polysaccharide Chemistry Present in LPS of outer membrane Metabolic product Gram– Source
  19. 19. Test for endotoxin presence Endotoxins are heat resistant, may persist on surfaces. LAL- Limulus Amoebocyte Lysate – presence of minute amounts of endotoxin lyses amoebocytes which release lysate Lysate then causes coagulation of the media
  20. 20. Cytopathic Effects of Viruses Table 15.4
  21. 21. <ul><li>Fungal waste products may cause symptoms </li></ul><ul><li>Chronic infections provoke an allergic response </li></ul><ul><li>Tichothecene toxins inhibit protein synthesis </li></ul><ul><ul><ul><ul><ul><li>(headaches, chills, nausea, vomiting, visual disturbances) </li></ul></ul></ul></ul></ul><ul><ul><li>Fusarium, Stachybotris (common molds) </li></ul></ul><ul><li>Proteases – modify host cell membranes </li></ul><ul><ul><li>Candida, Trichophyton (cutaneous mycoses) </li></ul></ul><ul><li>Capsule prevents phagocytosis </li></ul><ul><ul><li>Cryptococcus – (meningitis) </li></ul></ul><ul><li>Ergot toxin – LSD is a derivative </li></ul><ul><ul><li>Claviceps purpurea - grain </li></ul></ul>Pathogenic Properties of Fungi
  22. 22. <ul><li>Aflatoxin - carcinogenic </li></ul><ul><ul><li>Aspergillus </li></ul></ul><ul><li>Mycotoxins </li></ul><ul><ul><li>Neurotoxins: Phalloidin, amanitin </li></ul></ul><ul><ul><ul><li>Amanita – “Death cap mushroom” </li></ul></ul></ul>Pathogenic Properties of Fungi
  23. 23. <ul><li>Presence of protozoa and protozoan waste products may cause symptoms </li></ul><ul><li>Plasmodium ( malaria)- Invasion and lysis </li></ul><ul><li>Toxoplasma – are phagositized and survive in phagosome of macropahge </li></ul><ul><li>Avoid host defenses by </li></ul><ul><ul><li>Growing in phagocytes </li></ul></ul><ul><ul><li>Antigenic variation </li></ul></ul>Pathogenic Properties of Protozoa
  24. 24. <ul><li>Use host tissue for nutrients/incubation </li></ul><ul><li>Presence of parasite interferes with host function </li></ul><ul><li>Parasite's metabolic waste can cause symptoms </li></ul><ul><li>Wuchereria bancrofti roundworm - elephantiasis </li></ul><ul><li>Tapeworms, flukes </li></ul>Pathogenic Properties of Helminths
  25. 25. <ul><li>Neurotoxins produced by dinoflagellates </li></ul><ul><ul><li>Saxitoxin </li></ul></ul><ul><ul><ul><li>Paralytic shellfish poisoning </li></ul></ul></ul>Pathogenic Properties of Algae
  26. 26. <ul><li>Respiratory tract </li></ul><ul><ul><li>Coughing, sneezing </li></ul></ul><ul><li>Gastrointestinal tract </li></ul><ul><ul><li>Feces, saliva </li></ul></ul><ul><li>Genitourinary tract </li></ul><ul><ul><li>Urine, vaginal secretions </li></ul></ul><ul><li>Skin </li></ul><ul><li>Blood </li></ul><ul><ul><li>Biting arthropods, needles/syringes </li></ul></ul>Portals of Exit
  27. 27. Mechanisms of Pathogenicity Figure 15.9