Mechanisms of Pathogenicity

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Mechanisms of Pathogenicity

• Microbial Invasion of the Host

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To Cause Disease

• Gain Access
• Adherence
• Evade the Host Defense
• Damage

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Easy Access

• Inhale
• Touch
• Ingest
• Inject

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Access Portals of Entry

• Mucous membranes
• Thin layer of epithelial cells
• Covered with mucous
• Nice Warm and Moist!

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Access Portals of Entry

• Mucous membranes
• Respiratory
• GI
• Genitourinary tract
• Eyes

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Access Portals of Entry

• Skin
• Impenetrable to most organism
• Break or abrasion presents opportunity
• Microenvironments
• Sweat glands
• Hair follicles
• Boring Parasites
• Hookworm larvae

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Skin pg 559
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Usually the first sign of infection is itching,
and a rash at the site where skin touched
contaminated soil or sand, which occurs when the
larvae penetrate the skin, followed by anemia,
abdominal pain, diarrhea, loss of appetite, and
weight loss.
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Access Portals of Entry

• Parenteral Route
• Punctures
• Injections
• Bites
• Cuts
• Surgery

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Access Portals of Entry

• Preferred Portals of Entry
• Disease outcome depends on method of entry
• Streptococcus pneumoniae inhalation
• Salmonella typhi ingestion

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II. Adherence

• Colonize stick to a tissue surface
• Cell receptor and invader ligand
• Adhesins of invader (ligand)
• Glycoproteins or lipoproteins
• Varies with species of invader
• Receptors vary with tissue (cell type) of host
• Specific interaction

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III. Evading Host Defenses

• Number of invaders
• Sufficient to overcome immune system cells
• Varies with species of invader
• E coli (ETEC)108 cells
• Shigella 10-100 cells
• Mycobacterium tuberculosis 10 bacilli by
  inhalation
• U.S. Food and Drug Administration Bad Bug Book

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III. Evading Host Defenses

• Number of invaders
• Infectious Dose
• Measure of virulence
• ID50 amount given to test animals to cause
  infection in 50 of the recipients

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III. Evading Host Defenses

• Number of invaders
• Lethal Dose
• Measure of toxicity or virulence
• LD50 amount given to test animals to cause
  Death in 50 of the test animals

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III. Evading the Host Defenses

• Capsules
• Glycocalyx impairs phagocytosis by immune cells
• Recognition and adherence is impaired
• Antibodies can aid in phagocytosis
• Virulence factor
• S. pneumoniae capsule must be present to cause
  disease

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III. Evading the Host Defenses

• M-Protein
• Component of the cell wall
• Virulence factor of S. pyogenes
• Cell surface and fimbrae
• Aids in attachment
• Resistance to phagocytosis
• -opsonization inhibited

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Model of Streptococcal M Protein
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III. Evading the Host Defenses

• Antigenic Variation
• Slight change in structures that antibodies
  recognize

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III. Evading the Host Defenses

• Enzymes/toxins directed against immune cells
• Leukocidins
• Destroy WBC and Phagocytes
• Different forms
• Streptococcal leukocidin degrades lysozyme

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III. Evading the Host Defenses

• Enzymes
• Hemolysins
• Cause lysis of RBCs
• Partial or complete
• Gas gangrene

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III. Evading the Host Defenses

• Enzymes
• Streptolysin O
• SLOinactivated by oxygen
• Kill WBC, RBC
• Streptolysin S
• SLS
• Oxygen insensitive
• Kill WBC, RBC

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III. Evading the Host Defenses

• Enzymes
• Coagulases
• Clot blood
• Fibrinogen co-aggulation
• Protection by isolation

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III. Evading the Host Defenses

• Enzymes
• Kinases
• Dissolve blood clots
• Streptokinase
• Staphylokinase
• Spread infection
• New Drugs
• Treat heart attacks by removing coronary
  obstruction

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III. Evading the Host Defenses

• Enzymes
• Hyaluronidase and Collagenase
• Dissolves extracellular matrix
• Glue of tissues
• Spread infection
• IgA proteases
• Destroys IgA antibodies

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Collagen Triple Helix
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Damage to Host Cells

• Direct Damage to tissues and cells
• Bacterial Metabolism toxin
• Bacterial Entry/extrusion
• Iron sequestration

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Damage to Host Cells

• Bacterial Toxins
• Cause of most damage
• Primary factor contributing to pathogenicity
• Affects tissues away from point of origin

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Damage to Host Cells

• General Effects of Toxins
• Fever
• Shock
• Diarrhea
• Heart irregularities
• Destroy blood and immune cells and vessels

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Damage to Host Cells

• Exotoxins
• Produced and released by bacterial metabolism
• Proteins some catalytic
• Membrane channels
• Membrane destabilizers

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Damage to Host Cells

• Exotoxins
• Plasmid or phage encoded
• G, mainly
• Inhibit metabolic functions
• Subunit toxins
• 3 general types

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Damage to Host CellsExotoxins

• 1. Cytotoxin
• Kill Host cell
• Ex Diptheria Toxin (Corynebacterium diptheriae)
• Inhibits protein synthesis
• Inhibits GTP hydrolysis on ribosome
• No translocation
• Lysogenic Phage encoded
• b-tox, w-tox

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EF2 is site of ADP-Ribosylation
The second elongation factor, EF-G (EF-2), shunts
the ribosome along, again using GTP
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Damage to Host CellsExotoxins

• 1. Cytotoxin
• Kill Host cell
• Ex Streptococcsus exotoxin
• Cell lysis by insertion of protein channels
• Ex Clostridium perfringens
• Cell lysis by cell membrane disruption

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Damage to Host CellsExotoxins

• 2. Neurotoxins
• Interfere with nerve transmission
• Tetanus Toxin
• Clostridium tetani
• Binds nerve cells that control contraction cant
  relax
• Botulism toxin
• Clostridium botulinum
• Prevents nerve transmission at neuromuscular
  junction paralysis

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Damage to Host CellsExotoxins

• 3. Enterotoxin
• Cholera toxin
• Vibrio cholera chromosomal
• Enterotoxin
• E. coli plasmid
• Interfere with water and electrolyte balance
• Adenylate cyclase activated by toxin component
• Overproduction of cAMP

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Cholera toxin B subunit arrangement In cell
membrane
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Complement Activation
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Damage to Host Cells

• Endotoxins
• G- bacteria
• Part of cell wall
• Lipid A portion of LPS
• Release LPS upon cell death

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Damage to Host Cells

• Endotoxins
• Symptoms
• Fever
• Chills
• Weakness
• Shock
• Blood clotting