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. Learning Objectives
Upon completion of this chapter, you should be able to:
Identify the principle portals of entry and portals of exit
Use examples to explain how microbes adhere to host cells
Explain how capsules and cell walls contribute to pathogenicity
Compare the effects of coagulases, kinases, hyaluronidase, and collagenase
Define and give an example of antigenic variation
Describe how bacteria use the host cell’s cytoskeleton to enter the cell
Describe the function of siderophores
Provide an example of direct damage caused by bacteria and compare it to damage caused by release of a toxin
Contrast the nature and effects of endotoxins and exotoxins
Outline the mechanisms of A-B toxins, membrane-disrupting toxins, and superantigens.
Classify the following using type of toxin and effects on the body: Diptheria toxin, Erythrogenic toxin, Botulinum toxin, Tetanus toxin, Vibrio enterotoxin, and Staphylococcal enterotoxin
Differentiate between shock and septic shock
Using examples, describe the roles of plasmids and lysogeny in pathogenicity
List nine cytopathic effects of viral infections
Discuss the causes of symptoms due to infection with fungi, protozoans, helminthic, and algal pathogens

4. Mechanisms of Pathogenicity
Figure 15.9

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

6. Portals of Entry Mucous membranes Skin
Respiratory tract, GI tract, Genitourinary tract
Skin
Parenteral route (piercing skin or mucous membranes)
Every microbe has a preferred portal of entry!

7. Numbers of Invading Microbes
ID50: Infectious dose for 50% of the test population
LD50: Lethal dose for 50% of the test population

8. Bacillus anthracis Portal of Entry ID50 LD50 Skin 10–50 endospores
Unknown, but rarely lethal
Inhalation
10,000–20,000 endospores
Unknown, but high mortality rate
Ingestion
250,000–1,000,000 endospores
Unknown and rare, but high mortality rate

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

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

11. Adherence
Figure 15.1

12. Adherence
Figure 15.1

13. Adherence
Figure 15.1

14. 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?
Answer: adhesins/ligands – bind to host cell receptors

15. Virulence Contributors
Capsules
Cell Wall Components
Enzymes
Membrane Ruffling
Antigenic Variation
Penetration of Cytoskeleton

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

20. Membrane Ruffling
Figure 15.2

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. How Pathogens Damage Host
Using the host’s nutrients / Metabolizing the host
Direct Damage v. toxin damage

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

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

25. 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

26. Exotoxins and Endotoxins
Figure 15.4

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

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

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

30. Superantigens
Cause an intense immune response due to release of cytokines from host cells
Symptoms: fever, nausea, vomiting, diarrhea, shock, and death
Example: Exotoxin/enterotoxin produced by S. aureus

31. 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

32. Exotoxins & Lysogenic Conversion Cells only produce toxin when infected by bacteriophage; bacteriophage induces phenotypic change
Exotoxin
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

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

34. Endotoxins and the Pyrogenic Response
Figure 15.6

35. LAL Assay
Limulus amoebocyte lysate assay – tests for presence and amount of endotoxin
Amoebocyte lysis produces a clot
Endotoxin causes lysis
ANIMATION Virulence Factors: Endotoxins

36. Development of pathogenicity
Plasmids
Can carry R factors, toxins, code for production of capsules and fimbriae
Lysogenic conversion
Viral genome incorporation can carry virulence factors from other harmful bacteria, resulting in a weak strain becoming virulent.

37. 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?

38. Cytopathic Effects of Viruses
Growth inside of cells protects them from damage
Some viruses cause cytocidal (death) effects while other cause non-cytocidal (damage) effects
Examples: stopping mitosis, lysis, formation of inclusion bodies (viral parts), cell fusion (syncytium), production of interferons, antigenic changes in the host cell so they are not recognized by the body anymore, chromosomal changes (creating oncogenes), and transformation (cells don’t recognize boundaries anymore and divide uncontrollably)

39. Cytopathic Effects of Viruses
Figure 15.7

40. Cytopathic Effects of Viruses
Figure 15.8

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

42. Pathogenic Properties of Fungi
Ergot toxin – effects similar to LSD
Claviceps
Aflatoxin – potentially carcinogenic
Aspergillus
Mycotoxins
Neurotoxins: Phalloidin, amanitin
Amanita

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

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

45. Pathogenic Properties of Algae
Paralytic shellfish poisoning
Dinoflagellates
Saxitoxin; type of neurotoxin
Figure 27.13

46. 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