GENERAL ASPECTS OF

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GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture
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Faculty Dr. Alvin Fox
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Key Words
Pathogen Transmission Outbreak, Epidemic,
Pandemic Adhesion Normal flora
Penetration Infection Invasiveness/spread
Infectious diseases Extra/intra cellular
pathogen Compromised host Exotoxin Opportunisti
c infection Endotoxin - non-specific
immunity Nosocomial Specific immunity Kochs
postulates Autoimmunity Bioterrorism
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Pathogenicity

• virulence factors
• number of initial organisms
• immune status

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Pathogens

• The usual rate
• Oubreak - local
• Epidemic - regional/national
• Pandemic widespread (international)
• infections beyond the norm

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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

• normal flora
• environment
• often compromised individuals

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Opportunists - normal flora

• Skin
• Staphylococcus aureus
• Staphylococcus 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

• Community-acquired
• Nosocomial - hospital

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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
F-protein lipoteichoic acid
fibronectin
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E. coli
Fimbriae
Flagella
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E. coli fimbriae
Type 1
mannose
P

• galactose
• glycolipids
• glycoproteins

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Penetration and spread
Epithelium
Blood stream
Salmonella typhi
Salmonella enteritidis
Vibrio cholerae
Gut lumen
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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
Bacteria
Macrophage or neutrophil
Lysozome
Phagosome
Enter cytoplasm
Fusion
No fusion
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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-ribosylates elongation factor (EF2)
• inhibits protein synthesis
• kills cells, destroys tissues

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Cholera toxin and E. coli labile toxin

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

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• Shiga toxin - shigellosis
• Shiga-like toxin enterohemorrhagic E. coli
• lyses 28S 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 exotoxins

• 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 - endotoxin
• 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
• death or debilitation
• recognition
• clinically (e.g. common source clusters)
• clinical microbiology
• biodetection (environment)
• future