1. Microbial Mechanisms of Pathogenicity
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
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 deposited into 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 cells (100,000,000 cells)
ID50 for Inhalation Anthrax - 5,000 to 10,000 spores ????

13. ID50 and LD50 for Bacillus anthracis
Portal of entry
ID50
Skin
??? endospores
Inhalation
10,000-20,000 endospores
Ingestion
250,000-1,000,000 endospores

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 mutans Dextran (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 Beta 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 Exotoxin Source Mostly Gram + Metabolic product
By-products of growing cell
Chemistry
Protein
Water soluble
Fever? No
Neutralized by antitoxin
Yes
LD50
Small - Very potent
1 mg of Clostridium botulinum toxin can kill 1 million guinea pigs

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 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 Cholera enterotoxin
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 Exotoxin Lysogenic conversion • Corynebacterium diphtheriae
A-B toxin type III. Inhibits protein synthesis. +
• Streptococcus pyogenes
Membrane-disrupting. Type II Erythrogenic.
• Clostridium botulinum
A-B toxin. Neurotoxin - flaccid paralysis
Botox
• C. tetani
A-B toxin. Neurotoxin - prevents CNS inhibition - spastic paralysis
• Vibrio cholerae
A-B toxin. Enterotoxin. Stimulates cAMP to cause severe diarrhea
• Staphylococcus aureus
Superantigen. Type I. Enterotoxin.

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 Source Gram– Metabolic product
Present in LPS of outer membrane
Chemistry
Lipid
Fever?
Yes
Neutralized by antitoxin No
LD50
Relatively large

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