1. Microbial Mechanisms of Pathogenicity
Chapter 15
Microbial Mechanisms of Pathogenicity

2. Q&A
Almost every pathogen has a mechanism for attaching to host tissues at their portal of entry. What is this attachment called, and how does it occur?

3. How Microbes Enter a Host
15-1 Identify the principal portals of entry.
15-2 Define ID50 and LD50.
15-3 Using examples, explain how microbes adhere to host cells.

4. Mechanisms of Pathogenicity
Pathogenicity: The ability to cause disease
Virulence: The extent of pathogenicity

5. Portals of Entry Mucous membranes Skin Parenteral route
Preferred portal of entry

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

7. Bacillus anthracis Portal of Entry ID50 Skin 10–50 endospores
Inhalation
10,000–20,000 endospores
Ingestion
250,000–1,000,000 endospores

8. Toxins Portal of Entry ID50 Botulinum 0.03 ng/kg Shiga toxin 250 ng/kg
Staphylococcal enterotoxin
1350 ng/kg

9. Adherence Adhesins/ligands bind to receptors on host cells
Glycocalyx: Streptococcus mutans
Fimbriae: Escherichia coli
M protein: Streptococcus pyogenes
Form biofilms

10. Adherence
Figure 15.1

11. Adherence
Figure 15.1

12. Adherence
Figure 15.1

13. Q&A
Almost every pathogen has a mechanism for attaching to host tissues at their portal of entry. What is this attachment called, and how does it occur?

14. List three portals of entry, and describe how microorganisms gain access through each. 15-1
The LD50 of botulinum toxin is 0.03 ng/kg; the LD50 of Salmonella toxin is 12 mg/kg. Which is the more potent toxin? 15-2
How would a drug that binds mannose on human cells affect a pathogenic bacterium? 15-3

15. How Pathogens Penetrate Host Defenses
15-4 Explain how capsules and cell wall components contribute to pathogenicity.
15-5 Compare the effects of coagulases, kinases, hyaluronidase, and collagenase.
15-6 Define and give an example of antigenic variation.
15-7 Describe how bacteria use the host cell’s cytoskeleton to enter the cell.

16. Capsules Prevent phagocytosis Streptococcus pneumoniae
Haemophilus influenzae
Bacillus anthracis

17. Cell Wall Components M protein resists phagocytosis
Streptococcus pyogenes
Opa protein inhibits T helper cells
Neisseria gonorrhoeae
Mycolic acid (waxy lipid) resists digestion
Mycobacterium tuberculosis

18. Enzymes Coagulase: Coagulates fibrinogen Kinases: Digest fibrin clots
Hyaluronidase: Hydrolyzes hyaluronic acid
Collagenase: Hydrolyzes collagen
IgA proteases: Destroy IgA antibodies

19. Membrane Ruffling
Figure 15.2

20. Antigenic Variation Alter surface proteins
ANIMATION Virulence Factors: Hiding from Host Defenses
Figure 22.16

21. Penetration into the Host Cell Cytoskeleton
Invasins
Salmonella alters host actin to enter a host cell
Use actin to move from one cell to the next
Listeria
Figure 15.2

22. What function do capsules and M proteins have in common? 15-4
Would you expect a bacterium to make coagulase and kinase simultaneously? 15-5
Many vaccines provide years of protection against a disease. Why doesn’t the influenza vaccine offer more than a few months of protection? 15-6
How does E. coli cause membrane ruffling? 15-7

23. How Pathogens Damage Host Cells
15-8 Describe the function of siderophores.
15-9 Provide an example of direct damage, and compare this to toxin production.
15-10 Contrast the nature and effects of exotoxins and endotoxins.

24. How Pathogens Damage Host Cells
15-11 Outline the mechanisms of action of A-B toxins, membrane-disrupting toxins, and superantigens. Classify diphtheria toxin, erythrogenic toxin, botulinum toxin, tetanus toxin, Vibrio enterotoxin, and staphylococcal enterotoxin.
15-12 Identify the importance of the LAL assay.
15-13 Using examples, describe the roles of plasmids and lysogeny in pathogenicity.

25. Using the Host’s Nutrients: Siderophores
Use host’s iron
Figure 15.3

26. Direct Damage Disrupt host cell function Produce waste products Toxins
ANIMATION Virulence Factors: Penetrating Host Tissues
ANIMATION Virulence Factors: Enteric Pathogens

27. Of what value are siderophores? 15-8
How does toxigenicity differ from direct damage? 15-9

28. The Production of Toxins
Toxin: Substance that contributes to pathogenicity
Toxigenicity: Ability to produce a toxin
Toxemia: Presence of toxin in the host's blood
Toxoid: Inactivated toxin used in a vaccine
Antitoxin: Antibodies against a specific toxin

29. Exotoxins and Endotoxins
Figure 15.4

30. Exotoxins Specific for a structure or function in host cell
ANIMATION Virulence Factors: Exotoxins
Figure 15.4a

31. The Action of an A-B Exotoxin
Figure 15.5

32. Membrane-Disrupting Toxins
Lyse host’s cells by
Making protein channels in the plasma membrane
Leukocidins
Hemolysins
Streptolysins
Disrupting phospholipid bilayer

33. Superantigens
Cause an intense immune response due to release of cytokines from host cells
Symptoms: fever, nausea, vomiting, diarrhea, shock, and death

34. By-products of growing cell
Exotoxin
Source
Mostly Gram +
Relation to microbe
By-products of growing cell
Chemistry
Protein
Fever? No
Neutralized by antitoxin?
Yes
LD50
Small
Figure 15.4a

35. Exotoxins & Lysogenic Conversion
Lysogeny
Corynebacterium diphtheriae
A-B toxin +
Streptococcus pyogenes
Membrane-disrupting erythrogenic toxin
Clostridium botulinum
A-B toxin; neurotoxin
C. tetani
Vibrio cholerae
A-B toxin; enterotoxin
Staphylococcus aureus
Superantigen

36. Endotoxins Source Gram Relation to Microbe Outer membrane Chemistry
Lipid A
Fever?
Yes
Neutralized by Antitoxin? No
LD50
Relatively large
Figure 15.4b

37. Endotoxins and the Pyrogenic Response
Figure 15.6

38. LAL Assay Limulus amoebocyte lysate assay
Amoebocyte lysis produces a clot
Endotoxin causes lysis
ANIMATION Virulence Factors: Endotoxins

39. Inflammation Following Eye Surgery
Patient did not have an infection
The LAL assay of solution used in eye surgery
What was the cause of the eye inflammation?
What was the source?
Clinical Focus, p. 440

40. Differentiate an exotoxin from an endotoxin.
15-10
Food poisoning can be divided into two categories: food infection and food intoxication. On the basis of toxin production by bacteria, explain the difference between these two categories

41. Washwater containing Pseudomonas was sterilized and used to wash cardiac catheters. Three patients developed fever, chills, and hypotension following cardiac catheterization. The water and catheters were sterile. Why did the patients show these reactions? How should the water have been tested? 15-12
How can lysogeny turn the normally harmless E. coli into a pathogen? 15-13

42. Pathogenic Properties
15-14 List nine cytopathic effects of viral infections.
15-15 Discuss the causes of symptoms in fungal, protozoan, helminthic, and algal diseases.
15-16 Differentiate portal of entry and portal of exit.

43. Cytopathic Effects of Viruses
Figure 15.7

44. Cytopathic Effects of Viruses
Figure 15.8

45. Pathogenic Properties of Fungi
Fungal waste products may cause symptoms
Chronic infections provoke an allergic response
Tichothecene toxins inhibit protein synthesis
Fusarium
Proteases
Candida, Trichophyton
Capsule prevents phagocytosis
Cryptococcus

46. Pathogenic Properties of Fungi
Ergot toxin
Claviceps
Aflatoxin
Aspergillus
Mycotoxins
Neurotoxins: Phalloidin, amanitin
Amanita

47. Pathogenic Properties of Protozoa
Presence of protozoa
Protozoan waste products may cause symptoms
Avoid host defenses by
Growing in phagocytes
Antigenic variation

48. Pathogenic Properties of Helminths
Use host tissue
Presence of parasite interferes with host function
Parasite's metabolic waste can cause symptoms

49. Pathogenic Properties of Algae
Paralytic shellfish poisoning
Dinoflagellates
Saxitoxin
Figure 27.13

50. Portals of Exit Respiratory tract Gastrointestinal tract
Coughing and sneezing
Gastrointestinal tract
Feces and saliva
Genitourinary tract
Urine and vaginal secretions
Skin
Blood
Biting arthropods and needles or syringes

51. Mechanisms of Pathogenicity
Figure 15.9

52. Define cytopathic effects, and give five examples. 15-14
Identify one virulence factor that contributes to the pathogenicity of each of the following diseases: fungal, protozoan, helminthic, and algal
Which are the most often used portals of exit?