Pathogenicity: colonisation and evasion Flashcards

1
Q

Definitions:

  1. Pathogenicity
  2. Virulence
  3. Virulent bacteria
  4. Virulence factor/gene
  5. Housekeeping gene
A
  1. Ability of a microbe to cause a disease
  2. Degree of pathogenicity
  3. A bacterial that usually causes a disease when they infect
  4. Bacterial component/gene which is involved in pathogenesis
  5. Gene involved in all aspects of a bacteriums life
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2
Q

What are the 3 Koch’s postulates?

A
  1. Pathogen must occur in every cause of the disease and distribution corresponds to that of lesions observed (where we find the symptoms, we must be able to isolate the bacteria from here)
  2. Pathogen does not occur in healthy subjects
  3. After oblation and repeated growth of the microbe in a pure culture, pathogen can induce disease once placed into an animal (take pathogen, plate it out, back into animal and reintroduce disease)
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3
Q

How relevant are Kochs postulates in modern day?

A

A variety of diseases do not follow it due to:

  • cannot be grown in culture
  • no good animal model
  • disease throughout body but pathogen only found in one part of body
  • carries asymptomatically
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4
Q

What are the new updated postulates that are more relevant to modern knowledge?

A
  • The disease phenotype should be associated significantly more often with pathogenic organism than with non-pathogenic member or strain
  • Specific inactivation of gene(s) associated with the suspected virulence trait should lead to a measurable decrease in virulence
  • Restoration of full pathogenicity should accompany replacement of the mutated gene with the wild type original

(still requires a good animal model to test the postulates!)

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5
Q

What happens with mutagenesis with a pathogen?

A

Mutagenesis:

Take a wild type organism that is virulent - then identify virulence gene and remove this gene and reintroduce back in, we get a strain that is mutant and avirulent (lose virulence as the gene is lost).
Reintroduce the virulence gene - we then get the wild type phenotype and the virulent phenotype.

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6
Q

Where are virulence genes found in the pathogen?

A
  • Often encoded on mobile genetic elements
  • Thought to be relatively new DNA e.g. on plasmids, transposons, bacteriophages
  • Can be found in genomic islands
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7
Q

What are the 3 origins of virulence genes?

A
  1. Plasmids
    - adhesin genes
    - antibiotic resistance genes
    - toxin genes
  2. Bacteriophages
    - toxin genes
  3. Pathogenicity islands
    - toxin gene systems
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8
Q

What 4 factors define pathogenicity?

A
  • Transmission (must do this to be able to transfer disease)
  • Adherence (once into host, must be able to adhere to target)
  • Invasiveness (most ended to invade into underlying tissue to cause pathology)
  • Ability to cause damage
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9
Q

Explain the process of transmission of a microbe

A

Ways:

Inhalation (inhaling microbe through air)
Ingestion (faecal contamination)
Inoculation

Air borne transmission:
Several routes
Breathing out and being transferred in medium or large droplets
Through the footie route (droplets on surface which can be picked up)
Aerosol

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10
Q

Explain adherence in a microbe

A

How do microbes adhere?
- flagelle and fimbriae which have specialised surface proteins which help with the direct attachment

Signalling of surface proteins = triggers further protein expressed for adherence or to encourage eukaryotic cell to take up bacterial cell

Is adhesion always linked to virulence? No
Long term commensals also adhere
Adhesion may affect virulence and tissue tropism (which tissues the microbes will infect)

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11
Q

How do bacteria interact with eukaryotic cells?

A
  • Bacterium binds to eukaryotic surface
  • There is a change in gene expression within bacteria and induces signalling in eukaryotic cell
  • Gene expression in eukaryotic cell and production of compounds by host cell which could be anti-microbial peptides or could be markers involved in aiding further adhesion to uptake of the microbe by eukaryotic cell

Pathogenicity between host and bacterium requires signalling

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12
Q

Give the definitions of these:

  1. Contamination
  2. Colonisation
  3. Critically colonised
  4. Infection
A
  1. Microbes are present but not bound to surface
  2. Microbes adhere to surface
  3. More cells that get deeper into tissue
  4. Gross changes in host tissue resulting in disease
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13
Q

Why do microbes colonise?

A

Attachment to a surface
Source of nutrients (soluble, damage cells to obtain nutrients, nutrients obtained by host cell product)
Protective environment

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14
Q

What are the main factors that survival of a microbe depends on?

A
  • Depends on host function
  • Immune evasion needed - antigenic shift
  • Opposing immune function e.g. superoxide dimutase, inactive immune cells
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15
Q

How does invasiness work?

A

Starts with an epithelial cell. Microbe moves into this region and binds to survive and invaded into cells which line surface. Once invaded, it can get into underlying structures under the epithelial lining and transferred to other sites via the circulatory system to other organs.
Commonly goes to sites which has high blood supply such as the spleen, kidney and heart.

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16
Q

What are bacterial properties in aid invasion?

A
  1. secreted bacterial enzymes (these destroy tissue)
    - collagenase (Streptococcus pyogenes)
    - coagulase (Staphylococcus aureus)
    - Haemophilus leucocidins(Aa)
  2. antiphagocytic (to protect being phagocytosed)
    - capsule (Streptococcus pneumoniae)
    - M proteins (group A streptococci)
    - Fc (antibody) binding proteins - binds to Fc portion of antibody to prevent antibody from binding to compliment or from binding to Fc receptor on phagocytes
    - leukotoxins that kill macrophages
  3. toxins that control uptake mechanisms (prevent host taking it up by either making macrophages leaky or killing them)
17
Q

What are the two types of intracellular bacteria?

A

Obligate
- genuinely intracellular bacteria

Facultative
- pass through intracellular environments

18
Q

What are the mechanisms that intracellular bacteria invade a cell?

A
  • Phagocytosis
  • Induce = (makes use of endocytosis, through the bacterial surface proteins called invasins with host rectors that can activate the actin filaments underneath them and trigger this process. They may inject bacterial proteins into cytosol. All of these are complex interactions)
19
Q

How do intracellular bacteria survive once in the cell?

A
  • Modify phagosomal compartments
  • Escape the phagosome into the cytosol
  • Nullify the host response
20
Q

What type of intracellular microbes are virusus?

A

Obligate.

21
Q

Give the basic cycle of chlamydia which is an obligate bacteria

A

Chlamydia begins as an elementary body (outside cell) which is infectious but has no metabolism. This enters the cell and attaches to the cell, once inside the cell it triggers phagosome fusion. This cause the elementary body to change to the reticular body.
This reticulate body can then multiply. It is larger and metabolically active. Condensation of reticulate bodies changes then back into elementary bodies.
At 48h, the cell becomes dead and we get a mature inclusion in the cell which eventually lead to the extrusion of the infections bodies out of cell which then go on to infect other cells.

22
Q

Give some characteristics of obligate intracellular bacteia

A
  • Long generation time (not facing same environmental pressures that extracellular bacteria do)
  • Small size with small genome
  • Requires exogenous energy supply (no capable of generating ATP themselves)
  • May infect non-phagocytic cells
  • Protected from lysosomal degradation
  • Use own expression and replication mechanisms
  • No environmental reservoir
  • Cannot be grown by standard bacterial culture techniques
  • Difficult to study
23
Q

What happens to genome size in obligate bacteria?

A

Typically have small genome size in obligate intracellular bacteria.

This is because genes are only obtained if they are selected for.

This type of bacteria doesn’t need genes to survive in external environments so these genes are lost.

24
Q

What are some advantages of intracellular infection?

A
  • Immune evasion (avoids immune system)
  • Carriage around body (done by host)
  • Obtain nutrients from host
  • Smaller genome size
    (true of obligate bacteria, reductive evolution as there is a loss in genome size)
25
Q

Most common effect that immune system causes is inflammation:
Explain pyogenic inflammation

A
  • recognition of pathogen in innate immune system
  • Increases cytokines, neutrophils and bacterial killing
  • May push a response too far to cause tissue destruction
26
Q

What is a cytokine storm?

A

An over-activation of a healthy immune system leading to a massive production of cytokines.

Pro and Anti inflammatory cytokines are at highly increased levels.

Main cytokine increase is in TNFalpha and IL6.

Main effects are tissue damage, multiple organ failure, shock and death.

27
Q

What are 3 specific ways that the immune system can damage the body?

A
  1. Mimicry - inducing harmful antibody response
  2. Cytokine induction - cytokine storm
  3. Toxins that inhibit immune function
28
Q

Why are we not sure is pathogenicity is a mistake?

A

Not sure if pathogenicity is meant to occur if it is a side effect of pathogen existence.

(we have microbes in soil that are uninterested in being pathogens)