1. Mechanisms of microbial disease Schaechter et al, Chapter 9 Burton & Engelkirk Chapter 7

2. Not all microbes are pathogens “Normal” flora (endogenous, indigenous), resident or transient: commensal, symbiotic. Harmless, may be beneficial. –Outcompete pathogens –Provide necessary nutrients Skin: yeasts, mites, bacteria –Corynebacteria, propionibacteria –Staphylococcus spps, S. epidermis, S. aureus Intestine (enteric flora): 10 12 or more bacteria per gram feces

3. Bacteria of the GI Tract –Enterobacteria –Bacteroides –Escherichia coli –Bifidobacteria –Steptococci –Clostridia Large intestine pH 7-8 10 10 to10 12 per g Small intestine pH 7-7.5 10 5 to 10 8 per g Stomach pH 3 0 to 10 3 per g Duodenum, jejunum pH 6-7 0 to 10 4 per g

4. Opportunistic Pathogens –Pathogenic only under special circumstances: Susceptible host: Immune system weakened/compromised/suppressed Indigenous flora decreased (eg antibiotic treatment) “Indigenous” flora in the “wrong” location Frank Pathogens –Pathogenic at all times

5. Pathogenicity – ability to cause disease Virulence – extent or severity of disease Both depend on ability to infect the host and to cause damage Infection: –Colonization (usually at site of entry) Attachment and/or invasion (Adhesins or pili specific to receptors on target cell) –Multiplication of pathogen –Persistence of pathogen

6. Spread within initial host “Local” : pathogen confined to single area, usually point of entry “Systemic” or “generalized”: pathogen invades or is carried to other tissues, organs Latent infection Chronic infection Liver Duodenum

7. Target organs Location, environment –Consider route of exposure Specific attachment (by piliated pathogens) Hepatitis: HAV, HBV, HCV etc

8. Some Enteric Diseases Cholera Vibrio cholerae Typhoid fever Salmonella typhi Amebic dysentery Entamoeba histolytica Hepatitis Hepatitis A virus Norwalk disease Noroviruses Polio Polioviruses

9. Bacterial food poisoning Staphylococcus aureus Salmonella Clostridium

10. Airborne pathogens Respiratory viruses –Flu, parainfluenza, respiratory syncytial virus, common cold (rhinovirus) Bacteria –Legionnaire’s Disease (Legionella pneumophila ) Molds –Allergy, pneumonitis, mycosis, mycotoxicosis

11. Microbe is Extracellular Microbe secretes exotoxin –Botulinus, tetanus toxin (neurotoxins) –Enterotoxins (Cholera toxin, toxigenic E, coli, stimulate adenylate cyclase; Shigella toxin, cytotoxic; E. coli O157:H7, both) –Hemolysin, leukocidin, lecithinase Microbe secretes enzymes –Coagulase, kinases (fibrinolysin), hyaluronidase, collagenase Microbial membrane elicits reaction –Endotoxin, the lipopolysaccharide of the outer membrane of Gram-negative bacteria

12. Functional Damage Biochemical changes in host cell –Ion leakage, fluid leakage –Cholera toxin, targets intestinal epithelia –Lytic pores, S. aureus α-toxin Disruption/destruction of membrane Inhibition of protein synthesis –Diphtheria, Pseudomonas aeruginosa Inhibition of nerve function –Clostridium toxins, tetanus, botulinum

13. Microbe invades cell Cell membrane weakened by enzymes Fimbriae/pili allow attachment to cell wall – confers specificity for cell types

14. Intracellular Host cell killed: Lysis during replication Necrosis Apoptosis Immune system attacks infected cells

15. The cell cycle G1G1G1G1 S G2G2G2G2 M G0G0G0G0 Apoptosis, programmed cell death Mitosis (Cell division) A

16. Apoptosis vs necrosis APOPTOSIS In response to defined signals Follows defined sequence of events “Orderly shut-down” of cell functions Cell macromolecules recovered, recycled NECROSIS In response to non- specific damage Often starts with membrane destruction, events thereafter unpredictable Disorderly No recovery of contents

17. Course of infectious disease Exposure Entry Spread Multiplication Damage Immune response Outcome Infection Disease

18. Spread to new host Person-to-person spread –Communicable – no intermediate host –Contagious – easily transmitted (aerosol droplets, saliva) –Spread by contact – direct or via inanimate object (vehicle, fomite) Environmental spread: intermediate host, reservoir and/or vector may be involved

19. Animal Reservoirs Cryptosporidium parvum Single host, eg Beef, calves Oocyst Oocyst excysts, releases 4 sporozoites Sporozoites invade intestinal epithlial cells Sporozoites replicate asexually, differentiate into microgametes and macrogametes Sexual replication More oocysts ?

20. Comparison – viruses and bacteria Ability to infect Ability to spread Ability to invade Ability to cause damage Ability to survive outside host

21. Some viruses are carcinogens Epstein-Barr virus Herpesviruses –Nasopharyngeal carcinoma, Burkitt’s lymphoma

22. Prions “Infectious proteins” Creutzfeld-Jacob disease Bovine spongiform encephalopathy (BSE) –Template for protein misfolding Transmission ?