Bacteria Pathogenicity

1. Bacteria Pathogenicity Ability to Cause Infection

2. Infectious Diseases • Encounter-bug meets host (reservoir) • Bug adheres to host • Entry-bug enters host • Multiplication- bug multiplies in host

3. Infectious Diseases • Damage to host • Virulence of bug or host response • Outcome- bug or host wins or • Coexist- chronic infection

4. Reservoir • Exposure to microbe • Humans • Animals • Environment

5. Virulence Factors • Enhance colonization & growth • # of cells required to establish infection • Measure of pathogenicity

6. Adherence (Virulence Factor) • Attachment to host cells • Adhesins on pathogen (proteins) • Bind to complimentary surface receptor

7. Adherence • Prevent infection • Influenza changes adhesions over time • Neisseria gonorrhoeae -variety of adhesions

8. Portals of Entry • Mucous membranes • Respiratory • GI • Genitourinary • Conjunctiva

9. Portals of Entry • Skin • Bugs have preferred portal • C. tetani spores in soil --- anaerobic wound

10. Inoculum • Number of microbes-dose • Greater dose, more chance infection will occur • ID50 or LD50 expresses virulence • Infectious or lethal dose for 50% of population • LD50 used for toxins

11. ID50 • ID50 for B.anthracis via skin is 10 to 50 endospores • Via which route is infection more likely? • Via which route is infection more lethal?

12. Invasins • Adherence of microbe to surface • Activates factors that let microbe in-penetration • Microbes produce invasins (proteins) • Endocytosis

13. Colonization • Requires multiplication • Compete with normal flora for space & nutrients

14. Colonization • Overcome local host defenses • IgA (mucosal surfaces) • Avoid IgA • Rapid turnover of fimbriae/pili • Antigenic variation in type of pili • IgA proteases (enzymes) destroy IgA

15. Multiplication • Need Fe to multiply • Most is bound in host • Have own iron-binding molecules that compete for Fe-siderophores • \

16. Avoid Phagocytosis • Avoid recognition & attachment • Capsule • Impairs phagocytosis DT negative charges • Produce antibodies to capsule • \

17. Avoiding Phagocytosis • Components of cell wall –virulence • Mycolic acids in M. tuberculosis

18. Surviving Within Phagocyte • Escape from phagosome, vesicle, before fuses with lysosome • Prevent fusion with lysosome • Grow inside phagocyte protected from host

19. Tuberculosis • Ancient disease • 1/3 of world population infected • 8 million develop active TB each year • 2 million die each year • AIDs increases activation of latent TB

20. Tuberculosis • Dependent upon virulence of strain & host resistance • Produces cell mediated immunity which prevents active disease in many people • Multi drug resistance has developed

21. S & S of Pulmonary TB • Chronic disease • Progressive weight loss • Night sweats • Chronic cough • Hemoptysis

22. Mycobacterium tuberculosis • Acid fast bacillus (AFB) • Resistant to drying • Aerobic, slow growth • Airborne transmission

23. Mycobacterium tuberculosis • Inhale airborne droplets • Ingested by alveolar macrophages • Multiply in macrophages even with ongoing immune response

24. TB Response • Host immune response-delayed type hypersensitivity reaction • Tissue damage DT Inflammatory response

25. TB Conversion • TST skin reaction is positive • Occurs within 24 – 48 hours after exposure to TB antigens • Purified protein derivative of bacillus • Cell mediated immunity • Sensitized T cells react with proteins

26. QuantiferonGold • Blood test • Detects interferon gamma

27. How to Confirm Diagnosis • Sputum cultures for AFB smear & culture • Chest xray

28. Pathogenesis • LTBI (latent TB infection) • Immune defenses contain organism • Formation of tubercle • TB converter • No S&S of disease

29. Active Disease • Low resistance • Disease not controlled • Cytokines damage lung • Acute pulmonary infection • Can spread & cause death

30. TB Outcomes • Primary infection- positive skin test • 90% immune system controls infection via cellular immunity • TB germs isolated within tubercles( Activated macrophages)

31. TB Outcomes • 10% progressive primary infection-not controlled • Illness or death if not treated • Cavities in lungs • Spread throughout body

32. Secondary or Reactivation Infection • Reinfection-2nd exposure or • Bacteria escape immune system-reactivation • Activated macrophages release cytokines • Delayed hypersensitivity reaction

33. Prevention of Transmission • Negative pressure rooms • Respirator masks-fit tested • Admit staff aware of symptoms of TB • Yearly TST of staff • Conversions treated with 6-9 months of INH

34. Treatment • INH for LTBI or TB conversion • TB disease-active TB • 4 drugs till drug sensitivities return • DOT • 9- 12 months of treatment • Slow growing • Impedes abx entering cell wall

35. Resistant TB • MDR TB • Resistant to INH, & 1 other TB drug • XDR TB • Resistant to all 1st line drugs • Use 2nd line drugs for several years • Often leads to death • DT improper treatment

36. BCG • Live culture of M. bovis • Attenuated strain • Used in other countries to protect children from miliary disease • Can cause positive reaction on TST

37. Latent vs Active • Latent TB • Infected but no S&S • Not infectious • Active TB • S&S of disease • Infectious if pulmonary TB

38. Leprosy • Hanson’s disease- discovered in 1873 • Seen in tropics and underserved countries • U.S.-150 new cases per year

39. Leprosy • Infection of nervous system • Infects the peripheral nerves within skin • 2 forms of disease dependent upon immune response

40. M. leprae • Tuberculoid form • Regions of skin, lost sensation surrounded by nodules • Lose pigmentation • Causes strong cell mediated response • Activated macrophages keep microbe under control

41. Lepromatous Form • Weak immune response & microbe spreads • Skin & nerve cells infected • Shed large #s in nasal secretions and oozing sores-more infectious

42. Invasion via Enzymes • Exoenzymes- excreted to outside • Coagulases-clot fibrinogen in blood

43. Kinases • Breakdown fibrin • Produced by strep • Invades tissues & spreads • Used to isolate infections

44. Enzymes • Hyaluronidases – hydrolyzes hyaluronic acid (polysaccharide) • IgA proteases • Destroys IgA antibodies in secretions

45. Enzymes • Leukocidins • Kill neutrophils • Hemolysins-staph & strep • Dissolve RBCs • Able to obtain Fe

46. Invasion via Toxins • Toxins • Poisonous substances damage tissues • Cause shock, fever, inhibit protein synthesis • Two types • Exotoxins • Endotoxins

47. Exotoxins • Produced inside cell • Mostly proteins, kill in low concentrations • Mainly gram positive • Gene on plasmids or phages • Not bacterial genes

48. Exotoxins • Destroy part of cell or inhibit metabolic processes • Specific for each exotoxin • Toxin responsible for S &S of disease

49. Exotoxins • Antitoxins • Antibodies to toxin • Toxoid • Inactivated exotoxin • Use to induce immunity to toxins • Vaccines

50. A-B Toxins • 2 parts-polypeptides • A-active or enzyme component • B-binding component • B binds toxin to host cell • A-B toxin enters • Components separate & A kills host • Disrupts protein synthesis