1. Unit 4a – Almost done!

2. Chapter 15: Microbial Mechanisms of Pathogenicity
How microbes cause disease (figure 15.9)

3. Remember? Pathogenicity: The ability to cause disease.
Virulence: The extent of pathogenicity.

4. Most pathogens have a preferred portal of entry
Salmonella typhi swallowed vs. rubbed
Strep pneumonia inhaled vs. swallowed

5. Numbers of Invading Microbes
_____: Infectious dose for 50% of a sample population.
_____: Lethal dose (toxin) for 50% of a sample population.
actual number depends on:
virulence of pathogen
strength of host defenses
for same pathogen and same person, infective dosage varies from day to day with strength of body defenses
ID50

6. Clickers…
What is the LD50 for the bacterial toxin tested in the experiment below?
Dilution # of animals # of animals
mg/kg that died that survived

7. Adherence factors
for attachment to host cells

8. attachment by capsule
Remember Unit 1 discussion of Biofilms?

9. attachment by filaments

10. attachment by hook

11. attachment by viral spikes

12. Virulence factors: how pathogens cause disease
Many pathogens have multiple virulence factors
Virulence factors have 5 general effects
adherence to host cells
entering into host cells
destruction of host cells
avoiding phagocytosis
evading immune responses
Good Essay Question!

13. Some exoenzymes of virulence
1. collagenase: dissolves collagen (protein fibers in connective tissue); softens up a tissue so infection can spread
Clostridium’s spread of gas gangrene
2. IgA proteases
Destroy our IgA antibodies
Gonorrhoea and meningococcal meningitis can do
3. hyaluronidase: dissolves hyaluronic acid (glue-like substance that holds cells together); helps infection to spread
Streptococcus sp.

14. hyaluronidase dissolving hyaluronic acid

15. 4. lecithinase: dissolves cell membranes; pathogen can digest cell contents

16. enzymes of virulence
5. coagulases: clot blood; fibrin fibers coat pathogen, prevent phagocytosis
Staph (to wall off boils)
6. leukocidins: kill white blood cells
Staph aureus
7. kinases: dissolve clots (e.g. streptokinase)
8. hemolysins: cause hemolysis (lysis of red blood cells)
test for hemolysis on blood agar

17. alpha hemolysis: partial hemolysis, causes greenish zone around colony on blood agar

18. beta hemolysis: complete hemolysis, causes clear, colorless zone around colony

19. gamma hemolysis: NO hemolysis

20. Other virulence factors
_________: prevents phagocytosis, helps pathogen attach to host cell

21. Toxins Toxin: Substances that contribute to pathogenicity.
Toxigenicity: Ability to produce a toxin.
Toxemia: Presence of toxin in the host's blood.
Antitoxin: Antibodies our body produces against a specific toxin.
Toxoid: Inactivated toxin used in a vaccine.
When toxoids are injected as a vaccine, they stimulate antitoxin production so that immunity is produced
Diphtheria and tetanus toxoid vaccination

22. Exotoxins
Fig. 15.4

23. Endotoxins: Fig. 15.4

24. Endotoxins and the pyrogenic response figure 15.6

26. Sepsis and Septic Shock: pp. 639-641 (10th ed)
Although blood is normally sterile, if the defenses of the cardiovascular and lymphatic systems fail, microbes could enter blood/lymph
Septicemia: proliferation of pathogens in the blood
Fever
Sometimes causes organ damage
Sepsis: systemic inflammatory response syndrome (SIRS)
Mediators of inflammation into the blood stream
rapid heart or respiratory rates
High count of white blood cells
Lymphangitis: inflamed lymph vessels

27. Fig. 23.2 Relationship between the cardiovascular and lymphatic systems

28. Sepsis and Septic Shock continued
life-threatening systemic response to a bacterial infection
First stage is sepsis
Fever, chills and accelerated breathing & heart rate
Overwhelming infection leads to low blood pressure and low blood flow.
Shock
Vital organs, such as the brain, heart, kidneys, and liver may not function properly or may fail. Decreased urine output from kidney failure may be one symptom.
Severe sepsis to septic shock

29. Types
Gram-Negative Sepsis
Endotoxic shock
750,000 cases/ yr in US; at least 225,000 are fatal (textbook pg. 640)
Gram-Positive Sepsis
Staph, Strep & Enterococcus
Puerperal Sepsis
Childbirth fever
Nosocomial infection
Strep. pyogenes most frequent cause

30. high risk patients:
Burns
Age >60 or the very young
post-surgery (especially intestinal)
abdominal trauma
advanced cancer
diabetes

31. septic shock mechanism: pathogens release endotoxins, exotoxins:
these products stimulate release of chemicals from various host cells that produce the symptoms:
low blood pressure, especially when standing
rapid, weak pulse
fever (hypothermia in burn patients)
Low urine output
Agitation, confusion

32. septic shock symptoms: sudden high fever
disorientation, confusion, irritability, somnolence
edema (swelling): face, hands, feet
dyspnea
edema may constrict pharynx
bronchioles contract
death by asphyxiation may result
circulatory stagnation
inadequate blood volume causes low blood pressure, rapid weak pulse, possible total stagnation of bloodflow

33. septic shock treatment (not necessarily in this order)
inject epinephrine
open airway (intubation or tracheostomy)
oxygen if needed
restore blood volume: rapid IV
draw blood for blood gases and to culture pathogen
broad spectrum drug (until pathogen is known)
monoclonal antibodies against endotoxin

34. Back to figure 15.9

35. In summary: Damage to host cells
1. By using the host’s nutrients
Siderophores: proteins pathogens produce to get the iron they need from the host
2. By causing direct damage in the immediate vicinity of the invasion
3. By producing toxins

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