GENERAL ASPECTS OF

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GENERAL ASPECTS OF BACTERIAL PATHOGENESIS
Faculty Dr. Alvin Fox
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Key Words
Pathogen/Epidemic Adhesion Normal
flora Penetration Infection Invasiveness/spr
ead Infectious diseases Extra/intra cellular
pathogen Compromised host Exotoxin Opportunistic
infection Endotoxin (non-specific
immunity) Nosocomial Specific immunity Kochs
postulates Autoimmunity Transmission Bioterror
ism
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Pathogenicity

• virulence factors
• number of initial organisms
• immune status

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Pathogens

• Epidemics
• healthy people

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Koch's postulates

• isolated
• diseased not healthy people
• growth
• pure culture
• induce disease
• susceptible animals
• re-isolated
• susceptible animals

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Opportunistic infections

• compromised people
• normal flora
• environment

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Opportunists - normal flora

• Skin
• Staphylococcus aureus,
• S. epidermidis
• Propionibacterium acnes
• Intestine
• Bacteroides
• high numbers
• Enterobacteriaceae
• low number

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Opportunists - environment

• air
• water
• soil
• food

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Opportunists in hospital

• nosocomial

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Transmission

• airborne droplets
• food
• water
• sexual contact

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Host defenses

• Gut
• peristalsis
• defecation
• respiratory tract
• ciliary action
• coughing
• sneezing
• urogenital tract
• urination

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Adhesion
BACTERIUM
adhesin
receptor
EPITHELIUM
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S. pyogenes
lipoteichoic acid F-protein
fibronectin
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E. coli with fimbriae
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E. coli fimbriae
Type 1
mannose
P

• galactose
• glycolipids
• glycoproteins

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Penetration and spread
Epithelium
Salmonella typhi
Salmonella enteritidis
Vibrio cholerae
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Connective tissue destrction

• Helps bacterial dissemination
• collagenase
• hyaluronidase

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Extracellular pathogens

• resistant to extra-cellular killing
• killed on phagocytosis
• resist killing
• by avoiding internalization

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Protein A inhibits phagocytosis
PHAGOCYTE
Fc receptor
Protein A
immunoglobulin
BACTERIUM
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M protein inhibits phagocytosis
Complement
fibrinogen
M protein
peptidoglycan
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Intracellular parasite
lysozome
phagosome
No fusion
Fusion
Enter cytoplasm
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Killing of intracellular parasite

• Cell mediated immunity

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Tissue Injury

• exotoxins
• endotoxins and non-specific immunity
• - no antigen
• specific immunity
• - antigen

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Exotoxins

• proteins
• usually enzymes
• destroy cellular structures
• destroy extracellular matrix

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A-B toxins
Cell surface
Active
Binding
A
B
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• Diphtheria toxin and Pseudomonas exotoxin A
• ADP-ribosylate elongation factor (EF2)
• inhibit protein synthesis

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Cholera toxin and E. coli labile toxin
ADP-ribosylate adenylate cyclase cyclic AMP
active ion and water secretion diarrhea
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• Shiga toxin - shigellosis
• Shiga-like toxin - enterohemorraghic E. coli.
• lyses rRNA in ribosome
• death of epithelial cells
• poor water absorption
• diarrhea

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• 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

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Exotoxins - extracellular matrix of connective
tissue

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

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Membrane damaging toxins

• Proteases
• Phospholipases
• Detergent-like action

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C. perfringens phospholipase

• destroys blood vessels
• stops influx inflammatory cells
• creates anaerobic environment
• allows growth of this strict anaerobe.

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Exotoxins

• Antibodies (anti-toxins) neutralize
• vaccination

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Endotoxin

• lipopolysaccharide
• peptidoglycan -endotoxin-like action
• cell envelope components
• not proteins/enzymes

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Septic shock

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

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Endotoxins

• non-specific inflammation.
• cytokine release
• complement activation
• B cell mitogens
• polyclonal B cell activators
• adjuvants

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Specific immunity and immunopathology

• chronic infection
• tuberculosis
• leprosy
• syphilis
• persisting bacterial remnants
• autoimmunity

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IgA proteases

• help survival on external surfaces.
• H. influenzae
• S. pneumoniae
• N. gonorrhoeae
• N. meningitidis

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Bioterrorism

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