Virulence Factors Flashcards

1
Q

Koch’s postulates

A
  1. The bacterium must be found in all people with the disease in the correct location
  2. The bacterium should be isolated from the infected site and maintained in pure culture
  3. The pure culture should be capable of causing the disease
  4. The same bacterium should be isolated from the intentionally infected host.
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2
Q

Virulence

A

Ability of a bacterium to cause disease

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3
Q

Virulence Factor

A

A bacterial product or structure or strategy that contributes to virulence

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4
Q

Molecular Koch’s Postulates

A
  1. Gene present in virulent strain should be absent or inactive in avirulent strains
  2. Disrupting the gene in a virulent strain should diminish virulence or introducing the egen to an avirulent strain should make it virulent
  3. Gnese should be expressed during infection
  4. Antibodies to gene product should be protective
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5
Q

Example of afimbrial adhesion

A

Strep pyogenes has an adhesion protein F which binds to fibronectin - casting throat and wound infections

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6
Q

Explain evading complement

A
  • Attachment of sialic acid to the LPS O antigen alters LPS which is the main target for complement
  • bacteria produce proteins that bind to antibodies (e.g. Protein A by S.aureus) which bind to Fc portion and cause neutralisation
  • Loss of capsule - prevents opsonisation
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7
Q

Exotoxin

A
  • produced inside the cell (mostly gram +) and are secreted following lysis into surrounding medium
  • can be cytotoxic or specific
  • e.g. Chlorea toxin
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8
Q

Endotoxin

A
  • part of the outer portion of the cell wall of gram - bacteria (LPS)
  • liberated when cell dies or cell wall breaks apart
  • all gram - have LPS thus all have endotoxin in outer leaflet of outer membrane
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9
Q

Toxic component of LPS

A

Lipid A

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10
Q

Function of LPS

A
  • LPS binds to LPS -binding protein which triggers cytokine release which can lead to a cascade of event characterised as shock
  • shock can lead to MOSF
    *
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11
Q

What are the categories of exotoxins?

A
  1. A-B toxin (combo of A and B subunits; can be complex or simple)
  2. Membrane disrupting (pore-forming or membrane damaging)
  3. Superantigen (responsible for toxic shock)
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12
Q

Explain simple A-B toxins

A
  • produced as a single protein from a single gene
  • cleaved by host protease into A and B subunits
  • linked together by S-S bridge
  • A: active subunit
  • B: binding subunit - binds to target cell and delivers A subunit
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13
Q

Explain complex A-B toxins

A
  • 2 genes
  • A subunit proteolytically cleaved into A1 and A2 - held together by disulphide bridge
  • A1 subunit contains toxic activity
  • 1 A subunit: 5 B subunits
  • A2 subunit interacts with B subunits - delivers A1 to target cells
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14
Q

Types of membrane disrupting toxins

A
  1. Pore-forming - binds to receptor, inserts into membrane forming a pore, cell content leak out and cell dies (e.g. BT toxin)
  2. Phospholipases - cleaves phospholipid heads which destablises the membrane (e.g. Phospholipase A2)
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15
Q

Bioassay used to identify membrane-disrupting toxins

A

Hemolysins - lyse RBCs

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16
Q

Superantigens

A
  • Binds the MHC and TCR in the absence of an antigen
  • Tricks the T cell into thinking it has recognised a foreign antigen
  • Results in the increased activation of T-cells known as a cytokine storm
17
Q

Hydrolytic enzymes

A
  • enhance infection progression but not toxins
  • DNAse - reduces viscosity
  • Hyluronidase - causes tissue damage
18
Q

Ways of measuring virulence

A
  • LD50 - no. of cells to cause death in 50% animals
  • ID50 - no. of cells to cause infection in 50% animals
  • no. in organ
  • symptomology
  • luciferase - detects in real time
  • cultured cells

*a pathogen can have a low ID50 but high LD50 (or no LD50)

*ID50 will always be ≦ LD50

→ the lower the number the more virulent the organism

19
Q

Advantages and Disadvantages of using cultured cells to measure virulence

A

Advantages

  • human origin
  • cost efficient
  • defined
  • readily available
  • few ethical concerns
  • can measure adherence, cytotoxicity, invasion of pathogens

Disadvantages

  • incorrect gene expression
  • lack of polarisation
  • loss of traits overtime
  • often transformed as they are cancer-derived
  • cannot reproduce symptoms, organ specific traits, immune system response
20
Q

Virulence Strategies

A
  • production of toxins - tetanus, Botox
  • overcome body defences - vibrio
  • invade tissues and organs - diphtheria, salmonella