General Mechanisms of Bacterial Pathogenesis

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General Mechanisms of Bacterial Pathogenesis
-Bacterial strategies to host defense -Bacterial
toxins
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Colonization of host surfaces

• Penetrating intact skin
• Wound, surgery, arthropods
• Penetration of mucin layer
• Lack mucin receptor (not trapped)
• Mucin-degrading enzymes
• Movement between mucin strands
• Mucin layer thin over M cells (uptake bacteria)
• Resist to defensins
• LPS bind defense
• Peptidase degrade defensins
• Cytoplasmic proteins counter defensins

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Adherence

• Pili and fimbriae
• Tip binds receptor on host cell
• Pili constantly lost and reformed
• Different stages of infections
• Ag variation
• Signal transduction

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Colonization

• Biofilms
• Resistant to antibacterial agents
• sIgA protease
• Break hinge region
• Iron acquisition
• Siderophores

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Invasion of host cells

• Bacterial surface invasins
• Cause actin rearrangement in nonphagocytic cells
• Trigger host cells to engulf bacteria
• Taken up by phagocytes
• Prevent phagosome-lysosome fusion
• Escape from phogosome into cytoplasm
• Protect from Ab, complement and antibiotics
• Good source of nutrients
• Cell to cell spread
• Host actin mediated propel

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Capsules

• Network of polymers covering bacterial surface
• Usually polysaccharides
• Occasionally proteins
• Protect from complement activation
• Prevent formation of C3 convertase
• Protect from phagocyte-mediated killing
• Effective host response-Ab that bind capsule

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Additional survival strategies

• Resistant to nitric oxide
• LPS modification
• Sialic acid bound to O-Ag prevent formation of C3
  convertase
• O-Ag length change prevent MAC killing (serum
  resistance)
• Prevent migration of phagocytes
• Enzyme that degrades C5a
• Toxic proteins
• kill phagocytes
• Inhibit migration
• Reduce oxidative burst

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Surviving phagocytosis

• Escape phagosome
• Prevent phagosome-lysosome fusion
• Prevent acidification of vacuole
• Enzymes that detoxify reactive form of oxygen or
  prevent burst
• Catalase
• Superoxide dismutase

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Evading Ab response

• Surface Ag variation
• Alter pilus proteins
• Alter flagellar
• Capsule that resembles host molecules
• Hyaluronic acid
• Sialic acid
• Bacteria attach host proteins to surface
• Fc binding protein

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Opportunists

• Some but not all possess typical virulence
  factors
• Common in hospitalized or cancer patients
• Normal micorbiota or soil bacteria
• Usually present in high number over long period
  of time
• Take advantage of sites protected from immune
  system
• Often resist to multiple antibiotics

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Exotoxins

• Toxic bacterial proteins
• Based on target
• Neurotoxin, leukotoxin, hepatotoxin, cardiotoxin
• Based on type of activity
• ADP ribosylase, adenylcyclase, lecithinase,
  acetylase, AMPylation
• Based on organism
• Cholera, Shiga, diphtheria, botulinum, tetanus

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Toxin types

• Type I
• Bind target on cell surface
• Not translocated into the cell
• Example superantigens
• Type II
• Disrupt cell membrane
• Example phospholipaase, pore-forming cytotoxins
• Type III
• A-B toxins
• B binds receptor
• A translocated into cytoplasm
• ADP ribosylation
• Example diphtheria toxin, botulinum toxin

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Toxins and diseases

• Diphtheria toxin causes diphtheria
• Binds HB-EGF (abundant in heart)
• ADP ribosylates EF2 (type III)
• Botulinum toxin causes butulism
• Target neurons (type III)
• Cleave synaptobrevins (flaccid paralysis)
• Alpha-toxin contribute to gangrene
• Phospholipase activity (type II)
• Toxic shock syndrome toxin contribute to toxic
  shock syndrome
• Superantigen (type I)