Week 3: Bacterial Pathogenesis

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jlyip89
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Week 3: Bacterial Pathogenesis
Updated:
2014-01-27 23:44:47
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bacterial pathogenesis
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micro
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micro Week 3 Lecture
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  1. Pathogen
    a microorganism that is able to cause disease in a plant, animal or insect.
  2. PATHOGENICITY and VIRULENCE
    terms that refer to an organism's ability to cause disease
  3. infection
    the colonization and/or invasion and multiplication of pathogenic microorganisms in the host with or without the manifestation of disease
  4. Disease
    an abnormal condition of body function(s) or structure that is considered to be harmful to the affected host
  5. Acquisition of infectious agents (portal of entry)

    - name 3
    1. INGESTION

    2. INHALATION (spores)

    3. DIRECT PENETRATION

    • - Trauma or surgical procedure
    • - Needlestick
    • - Arthropod bite
    • - Sexual transmission
    • - Transplacental transmission
  6. General stages of bacterial infection
    • 1. colonization/adhesion
    • 2. invasion
    • 3. multiplication
  7. Bacterial colonization/adhesion

    - definition?
    - colonization factors
    - The successful occupation of a new habitat by a species not normally found in this niche

    • Colonization factors
    • –Fimbria

    –Glycocalyx (capsule and slime layer)

    –Teichoic acids and lipoteichoic acids (Gram +)

    –Adhesins
  8. Adhesins
    Bacterial surface proteins that bind to specific receptor molecules on the surface of host cells, sometime nonspecific

    •Enable a bacterium to adhere intimately to host cells in order to colonize and resist physical removal

    •Attractive vaccine candidates because they are often essential to infection and are surface-located, making them readily accessible to antibodies.
  9. Bacterial Invasion

    - definition?
    - invasion factors?
    - mech.
    • •The entry and spread throughout cells and/or
    • tissues of the host

    •Invasion factors (bacterial extracellular proteins): invasins

    –act locally to damage host cells and/or have the immediate effect of facilitating the growth and spread of the pathogen. The damage to the host as a result of this invasive activity may become part of the pathology of an infectious disease.

    –act against the host by breaking down primary or secondary defenses of the body
  10. Bacterial Multiplication

    - definition
    - influenced by?
    - multiplication factors?
    • - The ability of a microorganism to reproduce
    • during an infection; 

    - influenced by immunologic status, nutrient availability

    • Multiplication factors
    • –Bacterial substances to compete for iron and other nutrients (e.g., siderophores)

    –Bacterial ability to avoid being killed or removed by host immune mechanisms
  11. Bacterial ability to bypass or overcome host defense mech.
    • 1. Inhibition of phagocytosis
    • –multiple pathways

    • 2. Destruction of immune function
    • –Antigenic variation (Neisseria gonorrhoeae etc.)

    –Inactivation of antibody or complementation

    3. Intracellular growth (intracellular parasite)

    –Avoiding immune recognition (e.g., Mycobacteria, Francisellae, Brucellae Chlamydiae, Richettsiae etc.)
  12. Mech of Inhibition of phagocytosis
    1. inhibiting formation

    2. resistant to killing by lysosomes

    3. producing proteins that kill/damage phagocytes

    4. escape form the phagosome by lysing phagosome membrane

    5. Glycocalyx interferes opsonization
  13. Destruction of immune function

    - 2 mech.
    • - Periodically changing antigens (antigenic
    • variation); some bacteria avoid the host antibody response by changing from one type of fimbria to another, or by switching fimbrial tips

    - Produce proteases that degrade complement proteins and antibodies
  14. Intracellular growth ability
    (intracellular pathogen/parasite)
    • - Some bacteria can multiplicate/replicate
    • inside host cells (e.g., endothelial cells, fibroblasts, phagocytes)

    - protects the bacteria from immune clearance (e.g., antibody interaction with bacterial surface proteins )
  15. 2 Underlying mechanisms of bacterial pathogenicity
    1. Invasiveness (bacterial ability to invade cells/tissues)

    –colonization factors

    –Invasion factors

    –ability to bypass or overcome host defense mechanisms

    2. Toxigenesis (bacterial ability to produce toxins)

    Exotoxins: released from bacterial cells

    Endotoxins: cell-associated substances that are structural components of the cell walls of Gram-negative bacteria; lipopolysaccharide (LPS)
  16. Endotoxins
    part of the outer portion of the cell wall (Lipid A of LPS) of gram (-) bacteria

    - liberated when the bacteria die and cell wall breaks apart
  17. exotoxins
    - produced inside mostly gram (+) bacteria as part of their growth and metabolism

    - secreted or released following lysis into the surrounding medium
  18. LPS endotoxin

    - specific to gram (+) / (-)
    - inducer of ?
    - leads to?
    - only specific to gram (-)

    - powerful inducer of immune response and coagulation factor

    - leading to fever, sepsis, and shock
  19. 3 types of Exotoxins
    • 1. Toxins act on cell surface:
    • - binding to receptors
    • - forming spores

    • 2. Toxins that need to enter cell
      : A/B toxins

    3. Toxins directly delivered into host cell – Type III and IV secretion systems
  20. Superantigens
    •Bacterial exotoxins that stimulate T-cells independently of antigen

    •Mediate aberrant cross-linking of MHC II and T-cell receptor, resulting in activation of T-cells in absence of specific peptide.

    •Leads to massive release of cytokines, IL-1 and TNF, causing systemic reaction of fever, blood clots,  diarrhea, decreased blood pressure and shock.

    •The best characterized superantigens are the microbial toxins from Staphylococcus aureus and Streptococcus pyogenes, causing Toxic shock syndrome.
  21. A/B toxins
    Two subunits, A and B:

    B subunit binds to receptor

    A subunit is transferred into the interior of the cell
  22. Type III and IV secretion systems
    - Needle-like structure enables bacteria to inject exotoxins into host cells

    Secreted proteins (Yersinia bacterium)

    –YopH: dephosphorylate proteins required for phagocytosis

    –YopE; disrupt actin filaments

    –YopJ/P: initiate apoptosis of macrophage

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