Microbial Mechanisms of Pathogenicity

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

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. Exotoxin

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

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

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

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

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