MICROBIAL MECHANISMS OF PATHOGENICITY.

1. MICROBIAL MECHANISMS OF PATHOGENICITY. Introduction: How microorganisms enter a host.

2. MECHANISMS OF PATHOGENICITY.

3. PORTALS OF ENTRY. • Mucous membranes. • Skin. • Parenteral Route. • The Preferred Portal of Entry.

4. NUMBERS OF INVADING MICROBES. • The virulence of a microbe or the potency of its toxin is often expressed as the LD50. • LD50(lethal dose for 50% of hosts) is the the number of microbes in a dose that will kill 50% of inoculated test animals. • ID50:(infectious dose for 50% of hosts) is the dose required to produce a demonstrable infection in 50% of the test animals.

5. ADHERENCE. • Means attachment. • A necessary step in pathogenicity. • Attachment between pathogen and host is accomplished by means of adhesins or ligands. • Most adhesins of microbes are glycoproteins or lipoproteins.

6. ADHESINS ARE VERY DIVERSE. • S. mutans plays a key role in tooth decay attaches to the surface of teeth by its glycocalyx. • E. coli have adhesins on fimbriae that adhere only to specific kinds of cells. • N ghonorrhoeae has fimbriae containing adhesins which permit attachment to cells with appropriate receptors in the G.I tract.

7. HOW BACTERIA PENETRATE HOST DEFENSE • Capsules. • Components of the cell wall • M protein. • Enzymes: • Hemolysins. • Coagulases. • Hyaluronidase.

8. Collagenase. • Necrotizing factors. • Hypothermic factors. • Lecithinase.

9. HOW BACTERIA DAMAGE HOST CELLS. • Direct damage. • The production of Toxins: Toxin, Toxigenicity, Toxemia. • Types of toxins: Exotoxins and Endotoxins.

10. EXO and ENDOTOXINS.

11. ACTION OF AN EXOTOXIN.

12. EXOTOXINS. • Produced inside some bacteria as part of their growth and metabolism and released into the surrounding medium. • Are proteins, and many are enzymes. • Most bacteria that produce exotoxins are gram-positive. • The genes for most exotoxins are carried on bacterial plasmids or phages.

13. EXOTOXINS. • Are soluble in body fluids, so can easily diffuse into the blood and are rapidly transported throughout the body. • Work by destroying particular parts of the host’s cells or by inhibiting certain metabolic functions.

14. EXOTOXINS. • Three principal types: • Cytotoxins- kill host cells or affect their functions, e.g. Corynebacterium diphtheriae • This type of exotoxin binds to eF(elongation factors) in protein synthesis in the epithelial cells of the throat.

15. Neurotoxin. • Target the nervous system, and can interfere with normal nerve impulse transmission, e.g. C. tetani, C. botulinum.

16. ENTEROTOXINS. • Affect cells lining the gastrointestinal tract. • E.g. V. cholerae, C. difficile.

17. EXOTOXINS. • Are among the most lethal substances known. • Only 1mg of the botulinum exotoxin is enough to kill 1 million guinea pigs. • Are disease-specific. • Body produces antitoxins that provide immunity to exotoxins.

18. NOTABLE EXOTOXINS. • Diphtheria toxin. • Erythrogenic toxins. • Botulinum toxin. • Tetanus toxin • Vibrio Enterotoxin. • Staphylococcal Enterotoxin. • . • .

19. ENDOTOXINS • Part of the outer portion of the cellwall of gram negative bacteria. • Gram negative outer membrane consists of lipoproteins, phospholipids, and liposaccharides(LPS). • Lipid portion of LPS, called lipid A is the endotoxin. • Are liposaccharides.

20. Exert their effects when the gram negative bacteria dies and their cell wall undergo lysis, thus liberating the endotoxin(e.g use of antibiotics). • All endotoxins produce the same signs and symptoms. • Endotoxins can also induce miscarriage. • Can activate blood-clotting proteins(clots).

21. Shock. • Septic shock. • Organisms that produce endotoxin include: Salmonella typhi, proteus species, Neisseria meningitidis.

22. CPE EFFECTS OF VIRUSES. • CPE. • INCLUSION BODIES. • SYNCYTIA or GIANT CELLS.