Lecture 18: Trickery of Bacterial Pathogens Flashcards

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1
Q

What are the human-microbe relationships?

A
  1. Colonization of human host
    a. either as part of gut flora or harmony
    with the host
    b. or subverting host defences,
    causing disease
  2. Few microbes can invade tissues &
    prod toxic substances/inflict damage
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2
Q

Explain the production/delivery of various harmful factors?

A
  1. Organism needs to attach to hose tissue
  2. Need to replicate and evade immunity
  3. Damage host tissues to escape
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3
Q

What is the process of disease?

A
  1. Microbes cause disease whilst stealing:
    a. space
    b. nutrients
    c. and/or living tissue from host (e.g., us)
  2. How do they do this?
    a. Gain access to host (‘contamination’)
    b. Adhere to host (‘adherence’)
    c. Replicate on host (‘colonization’)
    d. Invade tissues (‘invasion’)
    e. Production of toxins, proteins, or other
    agents that cause host harm (‘damage’)
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4
Q

What are the 4 main mechanisms of bacterial pathogenicity? Give examples.

A
  1. Toxin ingestion following production
    a. Bacillus cereus
    b. not ingesting the pathogen, just its
    toxin
    c. sometimes associated with food
    poisoning
  2. Toxin production following
    colonization
    a. Clostridium botulinum
  3. Invasion of host tissues without toxin
    production
    a. Mycobacterium tuberculosis
  4. Tissue invasion followed by toxin
    production
    a. Vibrio cholerae
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5
Q

How do we know if a pathogen causes a specific disease?

A
  1. Robert Koch
    a. founder of public health
    b. developed koch’s postulates
  2. In 1800’s, discovered:
    a. Tuberculosis = Mycobacterium
    tuberculosis
    b. Cholera = Vibrio cholerae
    c. Anthrax = Bacillus anthracis
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6
Q

What must bacteria do for successful infection?

A
  1. Sense environment
    a. sense they’re inside the human host
    e.g., sensing the temperature (37)
  2. Need to know where they are…
  3. must express proteins to survive stress
  4. must express proteins required for
    adhesion or invasion
  5. May make toxins
  6. May enter host cell and replicate
  7. May spread through host cells
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7
Q

what is the ‘course’ of an infectious disease?

A
  1. Incubation period: interval between
    exposure and illness onset
  2. Illness phase: may still be infectious
    during incubation or convalescence
    phases
  3. Covalence phase: time of recuperation
    and recovery from illness
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8
Q

What are the principles of infectious disease/pathogenicity?

A
  1. Primary pathogen: microbe or virus that
    causes disease in healthy individual.
    a. E.g., plague, malaria, measles
  2. Opportunistic pathogen: causes disease
    only when body’s innate or adaptive
    defences are compromised or when
    introduced into unusual location
    a. Can be members of normal microbiota
    or common in environment
    (Pseudomonas)
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9
Q

What is meant by virulence?

What is meant by virulence factors?

A
  1. Refers to degree of pathogenicity

2. Allow microorganism to cause disease

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10
Q

What are the common virulence factors?

A
  1. Endotoxin
  2. Capsule
  3. Antigenic phase variation
  4. Sequestration of growth factors
  5. Resistance to serum killing
  6. Antimicrobial resistance
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11
Q

What are examples of virulence factors associated with specific pathogens?

A
  1. Exotoxin production
  2. Expression of adhesion factors
  3. Intracellular survival and manipulation
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12
Q

What is molecular Koch postulates

A

show that a gene found in a pathogenic microorganism encodes a product that contributes to the disease caused by the pathogen - virulence factor

   1. specific inactivation of gene(s) lead to 
      measurable loss in pathogenicity
   2. reintroducing gene should restore 
       pathogenicity
   3. gene causing virulence must be 
       expressed during infection
   4. immunity must be protective 
   5. phenotype or property under 
       investigation should be associated with 
       pathogenic members of genus
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13
Q

What are fimbriae?

A
  1. Key adherence factors
  2. How do cells avoid physical &
    immunological removal?
    a. adhere to cell surfaces and ECM
    b. Solid surfaces (e.g., teeth, heart valves)
    c. Other bacteria
  3. How do cells adhere?
    a. Often located at ends of fimbria or curli
    b. & other outer membrane proteins
  4. Adherence often combined with
    manipulation of host cell signalling and
    cytoskeleton (salmonella
    a. Adherence
    b. invasion
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14
Q

How do microorganisms scavenge iron?

A
  1. free iron is low in bodily fluids (it is
    bound to other things)
  2. Many different systems for
    scavenging:
    a. Siderophores chelate available iron
    & transport into bacteria
    b. scavenged direct from iron-binding
    proteins (e.g., lactoferrin-binding
    proteins)
    c. Often co-ordinately regulated
    d. Some pathogens avoid problem by
    cutting off need for iron (e.g.,
    Treponema pallidum - syphilis)
  3. Low level iron switches on aggressive
    virulence factors
    a. Diphtheria toxin (controlled by DtxR
    repressor)
    b. Shiga-like toxin
    c. Pseudomonas aeruginosa exotoxin
    A
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15
Q

How do microorganisms avoid phagocytosis?

A
  1. Capsule around them - avoids

recognition by phagocyte

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16
Q

How do pathogens damage the host?

A
  1. Exotoxins: proteins with specific
    damaging effects
    a. secreted or leak into tissue following
    bacterial lysis - foodborne intoxication
    = consumption - destroyed by heating
    b. act locally or systernically
    c. Proteins, immune system can generate
    Ab’s
17
Q

What are different types of exotoxins?

A
  1. Toxoids: inactivated toxins
  2. Antitoxin: suspension of neutralising Ab’s
  3. Neurotoxins: damage NS
  4. Enterotoxins: cause intestinal
    disturbance
  5. Cytotoxins: damage variety of cell types
18
Q

What are two parts of A-B toxins?

A
  1. A = active subunit, toxic, usually an
    enzyme
  2. B = binds to cell, determines affected
    cell type
    a. Structure of B subunit allows novel
    approaches for vaccines and therapies,
    can be used to deliver medically useful
    compounds to specific cell type
19
Q

What are endotoxins?

A
  1. other bacteria cell wall components
  2. Endotoxin: lipid A of LPS
  3. Lipid A triggers inflammatory response
    a. when localized helps clear infection
    b. When systemic, widespread response -
    septic shock or endotoxic shock
  4. lipid A released following cell lysis
  5. activates innate and adaptive defences
    a. toll-like receptors induce cytokine
    production; T-independent antigen
    response of B-cells at high
    concentrations
20
Q

What do endotoxins do to the host?

A
  1. fever
  2. Hypotension
    a. life-threatening complication of septicaemia
    b. endotoxic shock seen with intraveous equipment
  3. MOST EFFECTS OF ENDOTOXIN
    MEDIATED BY TUMOUR NECROSIS
    FACTOR
21
Q

What is EPEC

A
  1. one of many categories of diarrheagenic
    E. coli
  2. well established cause of human
    diarrhoea - particularly young children
  3. Hallmark of EPEC is A/E histopathology,
    often observed in small bowel biopsy
    specimens from infected patients
22
Q

What changes in host cells once infected by EPEC

A
  1. Formation of actin pedestals
  2. localized actin accumulation is so
    distinct it is the basis of vitro
    diagnostic test for EPEC
23
Q

What are type-3 secretion systems

A
  1. Essentially a needle
  2. Five components:
    a. Regulators
    b. Chaperons
    c. Secretion apparatus
    d. Translocators
    e. Effectors
  3. Five functions
    a. Export proteins across bacterial
    envelope
    b. Bring bacterial & host cells close
    together
    c. Translocate proteins between
    d. Translocated proteins across cell
    membranes
    e. Translocated proteins subvert host
    cell functions