1. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PowerPoint ® Lecture Slide Presentation prepared by Christine L. Case Microbiology B.E Pruitt & Jane J. Stein AN INTRODUCTION EIGHTH EDITION TORTORA FUNKE CASE Chapter 15 Microbial Mechanisms of Pathogenicity

2. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Microbial Mechanisms of Pathogenicity PathogenicityThe ability to cause disease by overcoming defenses of host VirulenceThe extent of pathogenicity

3. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Mucous membranes (respiratory, gastrointestinal, genitourinary, conjunctiva) Skin (follicles, sweat gland ducts) Parenteral route (punctures, injections, bites, cuts, wounds, surgery, splitting of skin) Respiratory tract – most common portal of entry Many organisms only cause infections when access their specific portal of entry Portals of Entry Identify the principal portals of entry.

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6. Virulence: ID 50 : Infectious dose for 50% of the test population LD 50 : Lethal dose (of a toxin) for 50% of the test population Numbers of Invading Microbes Define LD50 and ID50.

7. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Bacillus anthracis Portal of entryID 50 Skin10-50 endospores Inhalation10,000-20,000 endospores Ingestion250,000-1,000,000 endospores

8. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Adhesions/ligands ( surface projections) bind to receptors on host cells Glycocalyx (protective casing) Streptococcus mutans FimbriaeEscherichia coli M protein (virulence)Streptococcus pyogenes Opa proteinNeisseria gonorrhoeae Tapered endTreponema pallidum Biofilms – masses of microbes that can attach to living and nonliving surfaces (dental plaque, shower door scum) Adherence Using examples, explain how microbes adhere to host cells. Explain how capsules and cell wall components contribute to pathogenicity.

9. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Adherence

10. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings CoagulaseCoagulate blood (protect local infection in clot) KinasesDigest fibrin clots (spread from focal infection) HyaluronidaseHydrolyses hyaluronic acid that holds cells together CollagenaseHydrolyzes collagen (connective tissue) IgA proteasesDestroy IgA antibodies SiderophoresTake iron from host iron- binding proteins Antigenic variationAlter surface proteins, avoiding antibodies Enzymes Compare the effects of coagulases, kinases, hyaluronidase, and collagenase, and IgA proteases.

11. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Some pathogens can alter their surface antigens to avoid attack from host’s antibodies Influenza Gonorrhea African sleeping sickness Antigenic variation Define and give an example of antigenic variation. Describe how bacteria use the host cell's cytoplasm to enter the cell. Microbes produce surface proteins (invasins) that rearrange nearby actin filaments of the cytoskeleton of the host cell (microfilaments, microtubules) Salmonella (next slide)

12. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Penetration into the Host Cell Figure 15.2 Salmonella entering epithelial cells via invasins

13. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Siderophores Describe the function of siderophores. To obtain free iron, which is normally tightly bound, some pathogens secrete proteins called siderophores which remove iron from iron- transport proteins

14. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Toxins Direct damage – as pathogens metabolize and multiply in a cell, the cells often rupture (lyse) ToxinPoisonous substances that contribute to pathogenicity ToxigenicityAbility to produce a toxin ToxemiaPresence of toxin the host's blood ToxoidInactivated toxin used in a vaccine AntitoxinAntibodies against a specific toxin Provide an example of direct damages, and compare this to toxin production.

15. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Endotoxin Figure 15.4b Contrast the nature and effects of exotoxins and endotoxins.

16. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Exotoxins Figure 15.4a

17. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Endotoxins SourceGram– Metabolic productPresent in LPS of outer membrane ChemistryLipid Fever?Yes Neutralized by antitoxinNo LD 50 Relatively large

18. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Exotoxin SourceMostly Gram + Metabolic productBy-products of growing cell ChemistryProtein Fever?No Neutralized by antitoxinYes LD 50 Small

19. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings A-B toxins or type III toxins (diphtheria) Exotoxins Figure 15.5

20. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Superantigens or type I toxins Cause an intense immune response due to release of cytokines from host cells Fever, nausea, vomiting, diarrhea, shock, death Exotoxins

21. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Membrane-disrupting toxins or type II toxins Lyse host’s cells by: Making protein channels in the plasma membrane (e.g., leukocidins, hemolysins) Disrupting phospholipid bilayer Plasmids may carry genes for antibiotic resistance, toxins, capsules, and fimbriae Lysogenic conversion (new properties due to lysogenic phage) can result in bacteria with virulence factors, such as toxins or capsules Exotoxins

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23. Exotoxins Exotoxin Lysogenic conversion Corynebacterium diphtheriae A-B toxin. Inhibits protein synthesis. + Streptococcus pyogenes Membrane-disrupting. Erythrogenic. + Clostridium botulinumA-B toxin. Neurotoxin+ C. tetaniA-B toxin. Neurotoxin Vibrio choleraeA-B toxin. Enterotoxin+ Staphylococcus aureusSuperantigen. Enterotoxin.

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25. Endotoxins and pyrogenic (fever) response Endotoxins released by bacterial cell death, antibiotics, and antibodies Allow bacteria to cross blood-brain barrier LAL (Limulus ameobocyte lysate) assay used to detect endotoxins in drugs and on medical devices

26. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cytopathic Effects of Viruses Table 15.4

27. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Pathogenic Properties of Viruses Table 15.4 Viruses avoid host’s immune system by growing inside cells Viruses gain access due to attachment sites for receptors on the host cell CPE – cytopathic effects that are visible Cytopathic effects include: stopping mitosis lysis inclusion bodies cell fusion antigenic changes chromosomal changes transformations

28. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Inclusion body in brain of rabies victim Syncytium (giant cell) in cell infected with measles Cytopathic Effects of Viruses

29. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cluster of chick embryo cells (center) transformed by Rous sarcoma virus. Cluster from multiplication of single cell.

30. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Fungal symptoms caused by capsules, toxins, and allergic responses Fungal waste products may cause symptoms Chronic infections provoke an allergic response Tichothecene toxins inhibit protein synthesis Fusarium Proteases Candida, Trichophyton Pathogenic Properties of Fungi Discuss the causes of symptoms in fungal, protozoan, helminthic, and algal diseases.

31. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Capsule prevents phagocytosis Cryptococcus Ergot toxin Claviceps Aflatoxin Aspergillus Mycotoxins Neurotoxins: Phalloidin, amanitin Amanita Pathogenic Properties of Fungi

32. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Presence of protozoa Protozoan waste products may cause symptoms Avoid host defenses by Growing in phagocytes Antigenic variation (changing antigens) Pathogenic Properties of Protozoa

33. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Use host tissue Presence of parasite interferes with host function Parasite's metabolic waste can cause symptoms Pathogenic Properties of Helminths

34. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Neurotoxins produced by dinoflagellates Saxitoxin Paralytic shellfish poisoning Can cause paralysis Pathogenic Properties of Algae

35. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Respiratory tract Coughing, sneezing Gastrointestinal tract Feces, saliva Genitourinary tract Urine, vaginal secretions Skin Blood Biting arthropods, needles/syringes Portals of Exit Compare and contrast portal of entry and portal of exit.

36. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Mechanisms of Pathogenicity Figure 15.9