Chapter 15

1. Chapter 15 Microbial Mechanisms of Pathogenicity

2. Microbial Mechanisms of Pathogenicity • Pathogenicity The ability to cause disease • Virulence The extent of pathogenicity Many properties that determine a microbe’s pathogenicity or virulence are unclear or unknown But, when a microbe overpowers the hosts defenses, disease results! They need to gain entry, adhere, penetrate and cause damage to cause disease.

3. Disease: Pathogens may cause damage to host • Direct damage in the immediate vicinity • Grow and multiply and clog cells and passageways • Far removed from site of invasion by toxins • Toxins spread through blood and lymph • By hypersensitivity • The host’s reaction may cause the damage

4. Portals of Entry Entry of a Microbe • Need to adhere, penetrate, and then cause damage • Gain access via portal of entry and may a have preferred portal of entry - Streptococcus pneumoniae via GI tract? Small pox via vein? Portals of Entry: • Mucous membranes • Respiratory • GI • Urogenital • conjunctiva • Skin • Tough so rare - Necator americanus - hookworm • Parenteral route • Puncture or injection

5. Mucous Membranes: Respiratory • Respiratory Tract • microbes inhaled into mouth or nose in droplets of moisture or dust particles • Easiest and most frequently traveled portal of entry • Common cold • Flu • Tuberculosis • Whooping cough • Pneumonia • Measles • Strep Throat • Diphtheria

6. Mucous membranes: G.I. Tract • Salmonellosis • Salmonella sp. • Shigellosis • Shigella sp. • Cholera • Vibrio cholorea • Ulcers • Helicobacter pylori • Botulism • Clostridium botulinum Fecal - Oral Diseases • These pathogens enter the G.I. Tract at one end and exit at the other end. • Spread by contaminated hands & fingers or contaminated food & water • Poor personal hygiene.

7. Mucous Membranes of the Genitourinary System - STD’s Gonorrhea Neisseria gonorrhoeae Syphilis Treponema pallidum Chlamydia Chlamydia trachomatis HIV Herpes Simplex II

8. Mucous Membranes: Conjunctiva • Conjunctiva – • mucous membranes that cover the eyeball and lines the eyelid • Trachoma • Chlamydia trachomatis

9. 2nd Portal of Entry: Skin • Skin - the largest organ of the body. When unbroken is an effective barrier for most microorganisms. • Some microbes can gain entrance thru openings in the skin: hair follicles and sweat glands

10. 3rd Portal of Entry: Parenteral Microorganisms are depositedinto the tissues below the skin or mucous membranes • Punctures • injections • bites • scratches • surgery • splitting of skin due to swelling or dryness

11. Preferred Portal of Entry • Just because a pathogen enters your body it does not mean it’s going to cause disease. • pathogens - preferred portal of entry • Small pox via variolation • Streptococcus pneumoniae • if inhaled can cause pneumonia • if enters the G.I. Tract, no disease • Salmonella typhi • if enters the G.I. Tract can cause Typhoid Fever • if on skin, no disease

12. 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 • Example: ID50 for Vibrio cholerea 108 cells (100,000,000 cells) • ID50 for Inhalation Anthrax - 5,000 to 10,000 spores ????

13. ID50 and LD50for Bacillus anthracis

14. Key traits to a pathogen The ability to: • 1. Adherence • To host surfaces and not be washed off • 2. Avoid phagocytosis • Prevent host defenses from destroying • 3. Penetrate • Get into host and spread • 4. Produce Enzymes • Spread, prevent host defenses and cause damage at or near site of infection • 5. Produce Toxins • Cause damage at distant site

15. Adherence • Adhesions/ligands bind to receptors on host cells so won’t get flushed off. • Mechanisms to adhere and avoid host defenses: • Glycocalyx Streptococcus mutansDextran (plaque) • Waxes Mycobacteria • Fimbriae Escherichia coli • M protein Streptococcus pyogenes • Tapered end w/ hooks Treponema pallidum

16. Capsules Prevent phagocytosis and help with attachment (adherence) • Streptococcus pneumoniae • Klebsiella pneumoniae • Haemophilus influenzae • Bacillus anthracis • Streptococcus mutans • Yersinia pestis

17. Enzymes to help penetration Many pathogens secrete enzymes that contribute to their pathogenicity: • Increase virulence by use of enzymes • And avoid phagocytosis • Coagulase Coagulate blood - wall off from host make boil • Kinases Digest fibrin clot - allow spreading streptokinase and staphylolinase • Hyaluronidase Hydrolyses hyaluronic acid connective tissue • Collagenase Hydrolyzes collagen • IgA proteases Destroy IgA antibodies • Hemolysins lyse RBC’s

18. Hemolysins Alpha Hemolytic Streptococci • secrete hemolysins that cause the incomplete lysis or RBC’s Beta Hemolytic Streptococci - secrete hemolysins that cause the complete lysis of RBC’s

19. Leukocidins • Enzymes that attack certain types of WBC’s • 1. Kills WBC’s which prevents phagocytosis • 2. Releases & ruptures lysosomes • lysosomes - contain powerful hydrolytic enzymes which then cause more tissue damage

20. Enzymes: Necrotizing Factor “Flesh Eating Bacteria” Necrotizing fasciitis causes death (necrosis) to tissue cells

21. Summary of How Bacterial Pathogens Penetrate Host Defenses • 1. Adherence • 2. Capsule • 3. Enzymes • leukocidins • Hemolysins • Coagulase • Kinases • Hyaluronidase • Collagenase • Necrotizing Factor

22. Penetration into the Host Cell Figure 15.2

23. Toxins Provide properties to spread and cause damage to the host. Compare endotoxins and exotoxins • Endotoxins from inside the cell. Released upon cell lysis. • Exotoxins are secreted out of the cell during cell life. • Toxin Substances that contribute to pathogenicity • Toxigenicity Ability to produce a toxin • Toxemia Presence of toxin the host's blood • Toxoid Inactivated toxin used in a vaccine • Antitoxin Antibodies against a specific toxin

24. Exotoxins Mostly seen in Gram (+) Bacteria Most gene that code for exotoxins are located on plasmids or phages Figure 15.4a

25. Exotoxin

26. Exotoxins - three types • 1. Cytotoxins • kill cells • 2. Neurotoxins • interfere with normal nerve impulses • 3. Enterotoxins • effect cells lining the G.I. Tract Many toxins have A-B subunit toxins or type III toxins • A - active • Causes change in host • B - binding Figure 15.5

27. Exotoxins OR • Superantigens or type I toxins • Cause an intense immune response due to release of cytokines from host cells • Fever, nausea, vomiting, diarrhea, shock, death

28. Exotoxins • Membrane-disrupting toxins or type II toxins • Lyse host’s cells by: • Making protein channels in the plasma membrane (e.g., leukocidins, hemolysins) • Disrupting phospholipid bilayer Cholera • enterotoxin • Vibrio cholerae • Gram (-) comma shaped rods

29. Exotoxins

30. Botox • Botulism • Clostridium botulinum • Gram (+), anaerobic, spore-forming rod, found in soil • works at the neuromuscular junction • prevents impulse from nerve cell to muscle cell • results in muscle paralysis • Botulus – latin word for sausage (first known as sausage disease) C. botulinum does not grow in sausage today mainly due to nitrites added. Infant botulism 250 per yr., most associated with honey due to little microbial flora in G.I.

31. Tetanus (Lock Jaw) • Clostridium tetani • Gram (+), spore-forming, anaerobic rod • neurotoxin acts on nerves, resulting in the inhibition of muscle relaxation • Tetanospasmin - “spasms” or “Lock Jaw” • 50 cases a yr. in U.S. • 1 million per yr. Worldwide • 50% in newborns – because they dress severed umbilical cord with soil, clay or cow dung Tetanospasmin inhibits the release of acetylcholine by interfering with activity of cholinesterase (enzyme that normally breaks down acetylcholine)

32. Endotoxin Figure 15.4b

33. Endotoxins

34. Endotoxins - part of the Gram (-) Bacterial cell wall • LPS (Lipopolysaccharides) • O Antigen • Lipid A • Heat Stable (exotoxins are typically heat liable) • Lipid A - Toxin portion of the LPS • responsible for Fever that is associated with many Gram (-) Bacterial infections • Gram (-) cells are “digested” endotoxins are released - fever • Antibiotics • E. coli (0157:H7) • enterotoxin causes a hemolytic inflammation of the intestines • results in bloody diarrhea

35. Endotoxins Figure 15.6

36. Non bacteria pathogens • Viruses • Protozoa • Fungi • Algae • Helminths

37. Cytopathic Effects of Viruses Table 15.4

38. 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 • Ergot toxin • Claviceps

39. Pathogenic Properties of Fungi • Aflatoxin • Aspergillus on peanuts? • Mycotoxins • Neurotoxins: Phalloidin, amanitin • Amanita “death angel” - Liver damage

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

41. Pathogenic Properties of Helminths • Use host tissue • Presence of parasite interferes with host function • Parasite's metabolic waste can cause symptoms • Death can cause excessive immune reaction leading to more symptoms

42. Pathogenic Properties of Algae • Neurotoxins produced by dinoflagellates • Saxitoxin • Paralytic shellfish poisoning

43. Portals of Exit • Respiratory tract • Coughing, sneezing • Gastrointestinal tract • Feces, saliva • Genitourinary tract • Urine, vaginal secretions • Skin • Blood • Biting arthropods, needles/syringes

44. Mechanisms of Pathogenicity Figure 15.9