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GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture 41 . Faculty: Dr. Alvin Fox. Key Words. Pathogen Transmission Outbreak, Epidemic, Pandemic Adhesion Normal flora Penetration Infection Invasiveness/spread

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slide1

GENERAL ASPECTS OF

BACTERIAL PATHOGENESIS

Lecture 41

Faculty: Dr. Alvin Fox

key words
Key Words

Pathogen Transmission

Outbreak, Epidemic, Pandemic Adhesion

Normal flora Penetration

Infection Invasiveness/spread

Infectious diseases Extra/intra cellular pathogen Compromised host Exotoxin

Opportunistic infection Endotoxin - non-specific immunity

Nosocomial Specific immunity

Koch’s postulates Autoimmunity

Bioterrorism

pathogenicity
Pathogenicity
  • virulence factors
  • number of initial organisms
  • immune status
pathogens
Pathogens
  • The “usual” rate
  • Oubreak - local
  • Epidemic - regional/national
  • Pandemic – widespread (international)
    • infections “beyond the norm”
koch s postulates
Koch's postulates
  • isolated
    • diseased not healthy people
  • growth
    • pure culture
  • induce disease
    • susceptible animals
  • re-isolated
    • susceptible animals
opportunistic infections
Opportunistic infections
  • compromised people
    • normal flora
    • environment
opportunists normal flora
Opportunists - normal flora
  • Skin
    • Staphylococcus aureus
    • S. epidermidis
    • Propionibacterium acnes
  • Intestine
    • Bacteroides
      • high numbers
    • Enterobacteriaceae
      • low number
transmission
Transmission
  • airborne droplets
  • food
  • water
  • sexual contact
host defenses
Host defenses
  • Gut
    • peristalsis
    • defecation
  • respiratory tract
    • ciliary action
    • coughing
    • sneezing
  • urogenital tract
    • urination
adhesion
Adhesion

BACTERIUM

adhesin

receptor

EPITHELIUM

s pyogenes
S. pyogenes

F-protein

lipoteichoic acid

fibronectin

slide14

E. coli

Fimbriae

Flagella

e coli fimbriae
E. coli fimbriae

Type 1

mannose

P

  • galactose
    • glycolipids
    • glycoproteins
penetration and spread
Penetration and spread

Epithelium

Blood stream

Salmonella typhi

Salmonella enteritidis

Vibrio cholerae

Gut lumen

connective tissue destrction
Connective tissue destrction
  • Helps bacterial dissemination
    • collagenase
    • hyaluronidase
extracellular pathogens
Extracellular pathogens
  • resistant to extra-cellular killing
  • killed on phagocytosis
  • resist killing
    • by avoiding internalization
protein a inhibits phagocytosis
Protein A inhibits phagocytosis

PHAGOCYTE

Fc receptor

Protein A

immunoglobulin

BACTERIUM

m protein inhibits phagocytosis

r

r

r

M protein inhibits phagocytosis

Complement

fibrinogen

M protein

peptidoglycan

intracellular parasite
Intracellular parasite

Bacteria

Macrophage or neutrophil

Lysozome

Phagosome

Enter cytoplasm

Fusion

No fusion

killing of intracellular parasite
Killing of intracellular parasite
  • Cell mediated immunity
tissue injury
Tissue Injury
  • exotoxins
  • endotoxins and non-specific immunity
      • - no antigen
  • specific immunity
      • - antigen
slide24

Exotoxins

  • proteins
  • usually enzymes
  • destroy cellular structures
  • destroy extracellular matrix
a b toxins
A-B toxins

Cell surface

Active

Binding

A

B

slide26

Diphtheria toxin and Pseudomonas exotoxin A

    • ADP-ribosylates elongation factor (EF2)
    • inhibits protein synthesis
    • kills cells, destroys tissues
slide27

Cholera toxin and E. coli labile toxin

  • ADP-ribosylation of regulator
  • adenylate cyclase activation
  • cyclic AMP
  • active ion and water secretion
  • diarrhea
slide28

Shiga toxin - shigellosis

  • Shiga-like toxin – entero hemorrhagic E. coli
  • lyses 28S rRNA in ribosome
  • death of epithelial cells
  • poor water absorption
  • diarrhea
slide29

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
slide30

Exotoxins - extracellular matrix of connective tissue

  • Clostridium perfringens
    • collagenase
  • Staphylococcus aureus
    • - hyaluronidase
slide31

Membrane damaging exotoxins

  • Proteases
  • Phospholipases
  • Detergent-like action
slide32

C. perfringens phospholipase

  • destroys blood vessels
  • stops influx inflammatory cells
  • creates anaerobic environment
  • allows growth of this strict anaerobe.
exotoxins
Exotoxins
  • Antibodies (anti-toxins) neutralize
    • vaccination
endotoxin
Endotoxin
  • Lipopolysaccharide
  • peptidoglycan -endotoxin-like action
  • cell envelope components
  • not proteins/enzymes
slide35

Septic shock

  • hypotension (tissue pooling of fluids)
  • disseminated intravascular coagulation
  • fever
  • lack of effective oxygenation
  • overall system failure
endotoxins
Endotoxins
  • non-specific inflammation
  • cytokine release
  • complement activation
  • B cell mitogens
  • polyclonal B cell activators
  • adjuvants
specific immunity and immunopathology
Specific immunity and immunopathology
  • chronic infection
      • tuberculosis
      • leprosy
      • syphilis
  • persisting bacterial remnants
  • autoimmunity
slide38

IgA proteases

  • help survival on external surfaces
    • H. influenzae
    • S. pneumoniae
    • N. gonorrhoeae
    • N. meningitidis
bioterrorism
Bioterrorism
  • air
    • most common
  • no previous exposure
    • zoonoses
  • manifest initially
    • colds/flu-like
    • death
  • recognition
    • clinically (e.g. common source clusters)
    • clinical microbiology
    • biodetection (environment)
      • future