1. Bacterial Pathogenesis1

2. Pathogenicity virulence factors number of initial organisms
immune status 2 2

3. Pathogens The “usual” rate Oubreak - local
Epidemic - regional/national
Pandemic – widespread (international)
infections “beyond the norm” 3 3

4. Koch's postulates isolated growth induce disease re-isolated
diseased not healthy people
growth
pure culture
induce disease
susceptible animals
re-isolated 4 4

5. Opportunistic infections
immunocompromised patients
normal flora
environment 5 5

6. Opportunists - normal flora
Skin
Staphylococcus aureus,
S. epidermidis
Propionibacterium acnes
Intestine
Bacteroides
high numbers
Enterobacteriaceae
low number 6 6

7. Opportunists - environment
air
water
soil
food 7 7

8. Opportunists in hospital
Nosocomial (hospital aquired) 8 8

9. Transmission
airborne droplets
food
water
sexual contact 9 9

10. Host defenses Gut Respiratory tract Urogenital tract peristalsis
defecation
Respiratory tract
ciliary action
coughing
sneezing
Urogenital tract
urination 10 10

11. Adhesion
BACTERIUM
adhesin
receptor
EPITHELIUM 11

12. S. pyogenes
F-protein
lipoteichoic acid
fibronectin 12 12

13. E. coli
Fimbriae
Flagella 13 13

14. E. coli fimbriae Type 1 mannose P galactose glycolipids glycoproteins14 14

15. Penetration and spread
Epithelium
Blood stream
Salmonella typhi
Salmonella enteritidis
Vibrio cholerae 15
Gut lumen 15

16. Connective tissue destrction
Helps bacterial dissemination
collagenase
hyaluronidase 16 16

17. Extracellular pathogens
resistant to extra-cellular killing
killed on phagocytosis
resist killing
by avoiding internalization 17 17

18. Protein A inhibits phagocytosis
PHAGOCYTE
Fc receptor
immunoglobulin
Protein A
BACTERIUM 18 18

19. M protein inhibits phagocytosis
Complement
fibrinogen
M protein r
peptidoglycan 19 19

20. Intracellular parasite
Bacteria
Macrophage or neutrophil
Lysozome
Phagosome
Enter cytoplasm
No fusion
Fusion 20 20

21. Killing of intracellular parasite
Cell mediated immunity
T cells 21 21

22. Tissue Injury exotoxins endotoxins and non-specific immunity
- no antigen
specific immunity
- antigen 22 22

23. Exotoxins proteins usually enzymes destroy cellular structures
destroy extracellular matrix 23 23

24. A-B toxins
Cell surface
Active
Binding A B 24 24

25. Diphtheria toxin and Pseudomonas exotoxin A
ADP-ribosylates elongation factor (EF2)
inhibits protein synthesis
kills cells, destroys tissues 25 25

26. Cholera toxin and E. coli labile toxin
ADP-ribosylation of regulator
adenylate cyclase activation
cyclic AMP
active ion and water secretion
diarrhea 26 26

27. Shiga toxin - shigellosis
Shiga-like toxin – entero hemorrhagic E. coli
lyses 28S rRNA in ribosome
death of epithelial cells
poor water absorption
diarrhea 27 27

28. inhibits acetylcholine release inhibits nerve impulses
Botulinum toxin
inhibits acetylcholine release
inhibits nerve impulses
muscles inactive
flacid paralysis
Tetanus toxin
inhibits glycine release
inactivates inhibitory neurons
muscles over-active
rigid paralysis 28 28

29. Exotoxins - extracellular matrix of connective tissue
Clostridium perfringens
collagenase
Staphylococcus aureus
- hyaluronidase 29 29

30. Membrane damaging exotoxins
Proteases
Phospholipases
Detergent-like action 30 30

31. C. perfringens phospholipase
destroys blood vessels
stops influx inflammatory cells
creates anaerobic environment
allows growth of this strict anaerobe. 31 31

32. Exotoxins
Antibodies (anti-toxins) neutralize
vaccination 32 32

33. Endotoxin Lipopolysaccharide peptidoglycan -endotoxin-like action
cell envelope components
not proteins/enzymes 33 33

34. Septic shock hypotension (tissue pooling of fluids)
disseminated intravascular coagulation
fever
lack of effective oxygenation
overall system failure 34 34

35. Endotoxins non-specific inflammation cytokine release
complement activation
B cell mitogens
polyclonal B cell activators
adjuvants 35 35

36. Specific immunity and immunopathology
chronic infection
tuberculosis
leprosy
syphilis
persisting bacterial remnants
autoimmunity 36 36

37. IgA proteases help survival on external surfaces H. influenzae
S. pneumoniae
N. gonorrhoeae
N. meningitidis 37 37

38. Bioterrorism air no previous exposure manifest initially recognition
most common
no previous exposure
zoonoses
manifest initially
colds/flu-like
death
recognition
clinically (e.g. common source clusters)
clinical microbiology
biodetection (environment)
future 38 38