1. Medical Microbiology Chapter 19 Mechanisms of Bacterial Pathogenesis

2. Terms n Pathology – study of disease n Etiology – cause of disease n Pathogenesis – manner in which a disease develops n Infection – invasion or colonization of the body by pathogenic microorganisms n Disease – change from a state of health

3. Diseases n How are diseases catagorized? n Spread: –Communicable –Contagious –Noncommunicable n Categorization according to how often they occur in a given location: –endemic - constantly present –epidemic - disease occurring in excess of normal expectancy –Pandemic - worldwide epidemic

4. Disease n Severity or duration: –Acute –Chronic –Latent n Extent of infection: –Local infection –Systemic infection –Bacteremia, septicemia, toxemia, viremia

5. Disease n Primary infection vs. secondary infection n Subclinical infection

6. Spread of Disease n Etiology or etiological agent - cause of a disease n Reservoir - continual source of pathogens –human, animal, non-living n Mechanisms of Transmission: –contact transmission - from one person to another person n direct n indirect (through a fomite) n droplet (sneezing, coughing and talking)

7. Spread of Disease (cont.) –Vehicle Transmission - transmission of disease by a medium n water, food, air –Vector Transmission - transmission of disease by an insect n Nosocomial infections

8. Epidemiology n Epidemiology is the study of the frequency and distribution of disease –Examples

9. The CDC n The Centers for Disease Control and Prevention (CDC) is the nation’s center for epidemiology –The CDC tracks some 50 infectious diseases nationwide –they help county and state agencies during epidemics –The CDC publishes a weekly newsletter called Morbitity and Mortality Weekly

10. Virulence Factors n Successful pathogens have a variety of factors that contribute to their ability to cause disease –these are called virulence factors

11. Mechanisms of Pathogenesis n Successful pathogens carry out a sequence of events: –transmission to a susceptible host –gain access to the host –adherence to the target tissue –colonization and sometimes invasion –damage to the host –exit from the host –transmission to a new host

12. Mechanisms of Pathogenesis n Transmission –Contact, vehicle, vector, etc. n Access – Portals of Entry –Mucous membranes –Skin –Parenteral Route – through damage to the skin or mucous membranes –Table 19.1

13. Adherence and Invasion n Adherence: –Adhesins n Many are found on fimbriae n Table 19-2 –Capsules –Biofilms n Invasion – some pathogens can cross the mucous membranes

14. Colonization n Colonization – bacteria can evade the immune system and replicate to cause disease. –Antiphagocytic structures: n Capsule – extremely important virulence factor –They are also poorly antigenic (polysaccharides) n Cell walls (mycobacteria) –Intracellular growth –Antigenic variation – changing of antigens –Inactivation of antibodies or complement

15. Damage n Damage: –Enzymes –Toxins –Inappropriate Immune Responses n Exaggerated inflammation (endotoxin) n Cross-reactive antibodies - strep throat and rheumatic fever/glomerulonephritis

16. Enzymes n Enzymes are released from cells and damage host tissues –Leukocidins - kill white blood cells –Hemolysins - cause the lysis of RBCs  hemolysin - complete breakdown of RBCs  hemolysin - complete breakdown of RBCs  hemolysin - incomplete breakdown of RBCs  hemolysin - incomplete breakdown of RBCs –Streptokinase/Staphylokinase - breaks down blood clots n How could this be related to virulence?

17. Enzymes (cont.) –Coagulase - causes the formation of blood clots n almost all pathogenic strains of S. aureus produce this enzyme n How does this contribute to virulence? –Collagenase - breaks down collagen n produced by the clostridia that cause gas gangrene –Proteases, hyaluronidase, phospholipase C, etc.

18. Endotoxin n What is endotoxin? –the lipid A portion of lipopolysaccharide (LPS) n Fever - elevated body temperature n Vasodilation (leading to shock) n Inflammation n can even result in death

19. Exotoxins n These are substances released from bacteria that damage host tissues. n Cytotoxins - cause damage to cells –Erythrogenic toxins – (S. pyogenes) damage cells lining capillaries and cause blood to leak out under the skin (scarlet fever).

20. Exotoxins n Enterotoxins - cause damage to the gastrointestinal tract –diarrhea and vomiting –Caused by electrolyte loss (resulting in water loss into the large intestine) n Cholera and some E. coli infections (traveler’s diarrhea) – Figure 19-3 B n staphylococcal food poisoning

21. Exotoxins (cont.) –Some enterotoxins also kill the cells lining the intestines causing dysentery (bloody diarrhea) n bacterial dysentery (Shigella) and E. coli O157:H7 infections n Neurotoxins - inhibit the normal functioning of the nervous system –Tetanus toxin (Clostridium tetanii) blocks inhibitory nerve impulses that allow muscles to relax n Lock Jaw

22. Exotoxins (cont.) –Botulinum toxin (Clostridium botulinum) inhibits the functioning of motor neurons causing flaccid paralysis (muscles can’t contract) –1mg can kill 1,000,000 guinea pigs –Figure 19-3 C n Table 19-3

23. Superantigens n Superantigens - toxins that stimulate non- specific activation of T-cells –These then release large amount of cytokines leading to shock –toxic shock syndrome is caused by a superantigen produced by Staphylococcus aureus –can result in death –Figure 19-4