Bacterial Pathogenesis 1

Pathogenicity virulence factors number of initial organisms immune status 2 2

Pathogens The “usual” rate Oubreak - local Epidemic - regional/national Pandemic – widespread (international) infections “beyond the norm” 3 3

Koch's postulates isolated growth induce disease re-isolated diseased not healthy people growth pure culture induce disease susceptible animals re-isolated 4 4

Opportunistic infections immunocompromised patients normal flora environment 5 5

Opportunists - normal flora Skin Staphylococcus aureus, S. epidermidis Propionibacterium acnes Intestine Bacteroides high numbers Enterobacteriaceae low number 6 6

Opportunists - environment air water soil food 7 7

Opportunists in hospital Nosocomial (hospital aquired) 8 8

Transmission airborne droplets food water sexual contact 9 9

Host defenses Gut Respiratory tract Urogenital tract peristalsis defecation Respiratory tract ciliary action coughing sneezing Urogenital tract urination 10 10

Adhesion BACTERIUM adhesin receptor EPITHELIUM 11

S. pyogenes F-protein lipoteichoic acid fibronectin 12 12

E. coli Fimbriae Flagella 13 13

E. coli fimbriae Type 1 mannose P galactose glycolipids glycoproteins 14 14

Penetration and spread Epithelium Blood stream Salmonella typhi Salmonella enteritidis Vibrio cholerae 15 Gut lumen 15

Connective tissue destrction Helps bacterial dissemination collagenase hyaluronidase 16 16

Extracellular pathogens resistant to extra-cellular killing killed on phagocytosis resist killing by avoiding internalization 17 17

Protein A inhibits phagocytosis PHAGOCYTE Fc receptor immunoglobulin Protein A BACTERIUM 18 18

M protein inhibits phagocytosis Complement fibrinogen M protein r peptidoglycan 19 19

Intracellular parasite Bacteria Macrophage or neutrophil Lysozome Phagosome Enter cytoplasm No fusion Fusion 20 20

Killing of intracellular parasite Cell mediated immunity T cells 21 21

Tissue Injury exotoxins endotoxins and non-specific immunity - no antigen specific immunity - antigen 22 22

Exotoxins proteins usually enzymes destroy cellular structures destroy extracellular matrix 23 23

A-B toxins Cell surface Active Binding A B 24 24

Diphtheria toxin and Pseudomonas exotoxin A ADP-ribosylates elongation factor (EF2) inhibits protein synthesis kills cells, destroys tissues 25 25

Cholera toxin and E. coli labile toxin ADP-ribosylation of regulator adenylate cyclase activation cyclic AMP active ion and water secretion diarrhea 26 26

Shiga toxin - shigellosis Shiga-like toxin – entero hemorrhagic E. coli lyses 28S rRNA in ribosome death of epithelial cells poor water absorption diarrhea 27 27

inhibits acetylcholine release inhibits nerve impulses Botulinum toxin inhibits acetylcholine release inhibits nerve impulses muscles inactive flacid paralysis Tetanus toxin inhibits glycine release inactivates inhibitory neurons muscles over-active rigid paralysis 28 28

Exotoxins - extracellular matrix of connective tissue Clostridium perfringens collagenase Staphylococcus aureus - hyaluronidase 29 29

Membrane damaging exotoxins Proteases Phospholipases Detergent-like action 30 30

C. perfringens phospholipase destroys blood vessels stops influx inflammatory cells creates anaerobic environment allows growth of this strict anaerobe. 31 31

Exotoxins Antibodies (anti-toxins) neutralize vaccination 32 32

Endotoxin Lipopolysaccharide peptidoglycan -endotoxin-like action cell envelope components not proteins/enzymes 33 33

Septic shock hypotension (tissue pooling of fluids) disseminated intravascular coagulation fever lack of effective oxygenation overall system failure 34 34

Endotoxins non-specific inflammation cytokine release complement activation B cell mitogens polyclonal B cell activators adjuvants 35 35

Specific immunity and immunopathology chronic infection tuberculosis leprosy syphilis persisting bacterial remnants autoimmunity 36 36

IgA proteases help survival on external surfaces H. influenzae S. pneumoniae N. gonorrhoeae N. meningitidis 37 37

Bioterrorism air no previous exposure manifest initially recognition most common no previous exposure zoonoses manifest initially colds/flu-like death recognition clinically (e.g. common source clusters) clinical microbiology biodetection (environment) future 38 38