1. Mechanisms of Pathogenicity
Introduction
Entering the Host
Penetrating Host Defenses
Damaging Host Cells

2. Pathogenicity - Introduction
Pathogenicity is the ability of a pathogen to produce disease by overcoming host defenses
Virulence is the degree of pathogenicity
Expressed as LD50 (lethal dose necessary to kill 50% of the inoculated hosts)
ID50 is also used (dose necessary to infect 50% of the inoculated hosts)

3. Pathogenicity – Entering Host
Route of entry is called Portal of Entry
Usual portals include mucous membranes
Conjunctiva (eyes)
Respiratory tract
Gastrointestinal tract
Genitourinary tract

4. Pathogenicity – Entering Host
Respiratory most common
Microorganisms are inhaled on moisture droplets or dust particles
Genitourinary through mucous membranes and direct contact
Gastrointestinal through food, water and contaminated fingers

5. Pathogenicity – Entering Host
Most microorganisms cannot penetrate skin but can gain access through hair follicles and sweat ducts
Can gain entry through inoculation also called parenteral
insect bites
injections
wounds

6. Penetrating Host Defenses
Bacterial Elements that Overcome Host Defenses
Capsules
Cell Wall Components
Enzymes
Cytoskeletal Components

7. Penetrating Host Defenses
Capsules
Prevent or reduce phagocytosis
Usually polysaccharide
Examples
Dextran (S. mutans)
Polyglutamic acid (B. anthracsis)

8. Penetrating Host Defenses
Cell Wall Components
Adhesins (adhere to complementary receptors on host cells
Fimbriae – interact with membrane glycoproteins especially mannose
Some microbes reproduce only in host cells

9. Penetrating Host Defenses
Enzymes
Leukocidins – destroy white blood cells
Hemolysins – destroy red blood cells
Kinases – digest blood clots
Hyaluronidase – digests mucopolysccharides
Collogenase – destroy collogen of connective tissue

10. Penetrating Host Defenses
Via Cell Cytoskeleton
Invasins
Cause actin of microfilaments to form basket to carry bacteria into cell
Found in Salmonella

11. Damaging Host Cells Damage by metabolizing and reproducing in hosts
Damage by the production of toxins
Two major types of toxins
Endotoxins
Exotoxins

12. Damaging Host Cells Exotoxins Usually from Gram positive bacteria
Usually a secreted protein product
Heat Labile (60 to 80 deg C)
Very toxic – low LD50
Usually specific for cell type or cell function
Can be neutralized by antibodies
Symptoms usually appear sooner

13. Damaging Host Cells Exotoxins – Examples
Diptheria toxin –stops protein sysnthesis; damages heart and other organs
Cholera toxin – affects intestinal cells; disrups cAMP a cell secondary messenger
Tetnus toxin – affects nerve transmission
Toxic shock –affects T-cells & macrophages
Listeriolysin – pore forming cytotoxin allows cell to escape phagocytic vesicle

14. Damaging Host Cells Endotoxins Almost exclusively Gram negative
Present in LPS and released with destruction of cell
Heat stable – often can withstand autoclave
Not easily neutralized by antibodies
Produces general effects fever, aches, shock
Much larger LD50 than exotoxins

15. Damaging Host Cells Endotoxins – Examples
Salmonella typhi and typhoic fever-incubation period ~ 1 week symptoms due to LPS induced release of cytokines enter blood and multiply in spleen and liver
S. enteriditis & S. typhimurium – food borne gastroenterits – symptoms usually appear within 24 to 48 hours takes longer than with S. aureus exotoxin