1. Microbial Mechanisms of Pathogenicity

2. Virulence is the degree of pathogenicity of an organism.
Pathogenicity, Ability to cause disease.

3. Portals of entry are usually constant for a microbe
Mucous membranes of conjunctiva, respiratory, gut and genitals
Inhalation of dust and moisture particles to lungs
This is the most common entryway
Skin is hard to penetrate
Most enter through hair follicles and sweat ducts
Some fungi may attach to skin cells.

4. Microbes gain access to systemic system through
Bites
Injections
Wounds
Called parenteral rout

5. Preferred Portal of entry
Most cause infection only when they use a specific portal of entry
Example
Yersinia pestis by a number of portals
Streptococcus pneumoniae respiratory tract
Vibrio cholerae gut
Neisseria gonorrhoeae genitals
Clostridium perfringes parenteral

6. Lethal and infectious doses, the number of invaders determines what the outcome may be
LD50 # to kill 50% of inoculated individuals
ID50 # to cause infection in 50%
Is basically a method to compare relative toxicities or conditions

7. Bacillus anthracis Portal of entry ID50 Skin 10-50 endospores
Inhalation
10,000-20,000 endospores
Ingestion
250,000-1,000,000 endospores

8. Adherence In order to get into a host the bacteria must stick to it.
Surface projections (ligands) adhere to receptors on host cells.
Mostly on structures called fimbriae
The sugar mannose is the most common receptor.

9. Adherence Adhesions/ligands bind to receptors on host cells
Glycocalyx Streptococcus mutans
Fimbriae Escherichia coli
M protein Streptococcus pyogenes
Opa protein Neisseria gonorrhoeae
Tapered end Treponema pallidum

11. How Bacteria escape programmed host defenses
Capsules are extracellular glycocalyx material that surrounds the cell. Prevent recognition of the bacterial cell. Streptococcus pneumoniae
Cell wall components may also resist recognition and phagocytosis

12. Enzymes that protect Leukocidins destroy neutrophils and macrophages
Hemolysisn break up red blood cells
Coagulase prevents or breaks up blood clots designed to localize infection
IgA proteases Destroy IgA antibodies

13. Bacteria moving into tissues
Kinases- destroy blood clots
Hyaluronidase works on mucopolysaccharide that holds cells together
Collagenase hydrolyses connective tissue collagen
Invasins destroy cytoskeleton of individual cells.

14. How bacterial pathogens damage the host cells.
Only some of the cell damage is caused by bacteria themselves
Some bacteria enter the host cell and damage as they leave
Some bacteria harm the cell as they enter

15. Penetration into the Host Cell
Figure 15.2

16. Bacteria Toxins Cause the most damage
Toxins: poisonous substances produced by microbes
Toxigenicity: capacity of a microbe to produce toxin
Toxemia: presence of toxins in the blood
Toxoid: Inactivated toxin used in a vaccine
Antitoxin:Antibodies against a specific toxin

17. Exotoxins:
Produced by bacteria and released into surrounding area. Causes Disease
Cytotoxin or diphtheria toxin inhibits protein synthesis
Tetanus toxin prevents nerve transmission
Enterotoxins promote electrolyte and fluid loss from cells.
Neurotoxins (Botulinum toxin) prevent nerve transmission
Antibodies produced in response are antitoxins

18. By-products of growing cell
Exotoxin
Source
Mostly Gram +
Metabolic product
By-products of growing cell
Chemistry
Protein
Fever? No
Neutralized by antitoxin
Yes
LD50
Small

19. Exotoxins
A-B toxins or type III toxins
Figure 15.5

20. 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

21. 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

22. Exotoxins Exotoxin Lysogenic conversion • Corynebacterium diphtheriae
A-B toxin. Inhibits protein synthesis. +
• Streptococcus pyogenes
Membrane-disrupting. Erythrogenic.
• Clostridium botulinum
A-B toxin. Neurotoxin
• C. tetani
• Vibrio cholerae
A-B toxin. Enterotoxin
• Staphylococcus aureus
Superantigen. Enterotoxin.

23. Endotoxins
Figure 15.6

25. Endotoxins
Are structures of the bacterium itself that cause the disease, like lipopolysaccharide (LPS) of gram negative bacteria
May be released when cells are killed by antibiotics
Cause fever and shock
May allow the bacteria to cross the blood brain barrier

26. A test for endotoxins.
Limulus amoebocyte lysate (LAL) used to detect endotoxins in drugs and on medical devices.
The amoebocyte will lyse in the presence of endotoxins causing a thickening of the media.

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

28. Extra genetic material
Some bacteria may carry extra genes that help pathenogenisity
Plasmids (extra chromosomal) can carry genes for antibiotic resistance, toxins, capsules and fimbriae
Coagulase produced by Staphylococcus aureus
Fimbria in specific straines of E. coli

29. Pathogenesis of nonbacterial microbes
Viruses
Avoid immune system by growing inside host cell
May cause cell death or damage by growing and being released from the cell.
Casuse membranes to fuse
Fungi, Protozoa, Helminths and Algae
Symptoms caused by mixture of capsules, toxins, waste products and allergic response to the organism
Antigen switching allows to avoid hose immunity
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

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

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