Pathogenicity I

Question 1

what is pathogenicity?

Answer 1

Ability to cause disease

Question 2

what is virulence?

Answer 2

Degree of pathogenicity

Question 3

what is virulent bacteria?

Answer 3

Usually cause disease when they infect

Question 4

what is virulence factor/gene?

Answer 4

Bacterial/component only involved in pathogenesis

Question 5

what is the housekeeping gene?

Answer 5

Gene involved in all aspects of a bacterium’s life.

Question 6

what is koch’s postulates?

Answer 6

• Pathogen occurs in every case of the disease and distribution corresponds to that of lesions observed.
• Pathogen does not occur in healthy subjects
• After isolation and repeated growth in pure culture, pathogen can induce disease in susceptible animals.

Question 7

what is molecular koch’s postulates?

Answer 7

• 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

Question 8

what is virulent genes?

Answer 8

Often encoded on mobile genetic elements, bits of DNA that can be swapped between microbes.

Question 9

where do virulence genes originate from?

Answer 9

Plasmids:
* adhesin genes – plasmid to bind more easily
* antibiotic resistance genes
* toxin genes
Bacteriophages: toxin genes
Pathogenicity islands convey a toxin gene systems

Question 10

what factors define bacterial pathogenecity?

Answer 10

• Transmission – must be able to be transmitted to cause disease
• Adherence – once enter the host must be able to the target
• Invasiveness – sometimes, some pathogens can cause pathology without invading the underlying tissue. A lot of microbes need to invade.
• Ability to cause damage

Question 11

how are microbes transmitted?

Answer 11

1. Inhalation of pathogen
2. Ingestion: Faecal contamination
3. Inoculation:
   * contaminated needles and blood transfusions
   * skin contact
   * insects
   * sexual contact

Question 12

how do microbes adhere?

Answer 12

1. flagellae (also for motility) structures in their outer wall
2. fimbriae (pili) structures in their outer wall
3. specialised surface proteins: direct attachment or signalling to the eukaryotic cell to trigger further adhesion or even to encourage the eukaroytic cell to indigest the bacteria cell

Question 13

Is adhesion always linked to virulence?

Answer 13

No, as long term commensals also adhere. However adhesion may affect virulence and tissue tropism (which particular tissue a microbe will infect).

Question 14

how do bacteria interact with cells?

Answer 14

1. Bacterium binds to eukaryotic surface through it fimbriae/pili. This then leads to a signal and a change in gene expression with the bacteria.
2. Also induced signalling within the eukaryotic cell which leads to gene expression within that eukaryotic cell and production of compounds by the host cell.
3. The compound could be either antimicrobial peptides or they could be markers which are involved in enabling further adhesion or uptake of the microbe by the eukaryotic cell.

Question 15

what is colonisation?

Answer 15

Colonisation = Presence of microbes without accompanying disease

Question 16

what is infection?

Answer 16

Infection = Presence of microbes resulting in disease critical colonization which lead to infection. This infection can be local or systemic.

Question 17

how does microbe colonise ?

Answer 17

Colonisation happens through an attachment process.

Question 18

why does microbes colonise?

Answer 18

A microbe would want to colonise a host for a source of nutrients:
* May receive nutrient from the waste products of the host
* More protected environment in the host
* soluble
* damage cells to obtain release

Question 19

how does microbes survive?

Answer 19

• immune evasion - antigenic shift which is conducted by the Neisseria and Borrelia species
• oppose immune function eg superoxide dismutase, to inactivate immune cells

Question 20

what properties aid microbe invasion?

Answer 20

Secreted bacterial enzymes
Antiphagocytic (protect themselves from pahgocytosis)
Toxins that control uptake mechanisms control

Question 21

How do microbes enter the cell?

Answer 21

Phagocytosis - Induce uptake by macropinocytosis or endocytosis.

Question 22

how do bacteria survive the conditions?

Answer 22

• Modifies the phagosomal compartment
• Escape the phagosome into the cytosol
• Nullify host response

Question 23

how does chlamydia spread?

Answer 23

1. Has a dimorphic life cycle exists in two forms. It starts if as a elementary body which is infectious but had no metabolism, it is metabolically inert.
2. Attaches to cells and enters the cell.
3. Once within the cell its triggers phagosome fusion. This phagosome fusion cause the reorganisation of the elementary body into a reticulate body.
4. This reticulate body start to replicate it is not infectious so not capable of gaining entry into another cell however is metabolically active.
5. Once it reaches a certain critically mass condensation of reticulate bodies into elementary bodies.
6. Extrusion and release of infectious elementary body to infect other cells.

Question 24

what is rickettsiae?

Answer 24

Obligate intracellular bacteria it is a Gram negative bacilli. This microbes replicates in the cytosol of host endothelial cells.

Question 25

what is the features of obligate intracellular bacteria?

Answer 25

• Long generation time
• Small size with small genome
• Require exogenous energy supply
• May infect non-phagocytic cells
• Protected from lysosomal degradation
• Use own expression and replication mechanisms
• No environmental reservoir – acquired from other hosts
• Cannot be grown by standard bacterial culture techniques
• Difficult to study

Question 26

what are the advantages of intracelluar infection?

Answer 26

• immune evasion – hiding from immune system cannot be caught
• carriage around body by host cells
• obtain nutrients from host
• smaller genome size
  – especially true of obligate intracellular bacteria
  – (500-1000 genes vs 1500-6000 for free living bacteria)
  – reductive evolution
• loss of metabolic pathways
• defined ecological niche

Question 27

what is a cytokine storm?

Answer 27

• Over-activation of a healthy immune system can lead to massive production of cytokines
• Pro- and anti-inflammatory cytokines appear at highly increased levels in serum
• Main cytokine participants are TNFα and IL-6
• Main effects are tissue damage, multiple organ failure, shock and death
• Main pathology in Sepsis and septic shock.

Question 28

what is minicry?

Answer 28

we seen this commonly in group A b-haemolytic streptococci (anti-heart) the microbe mimic something in the host which then induce harmful antibody response not only to the pathogen but also to the host.

Question 29

what is cytokine induction?

Answer 29

• superantigens inappropriately inactivate immune response leading to shock (next lecture)
• LPS activates immune cells, inducing ‘cytokine storm’ - Sepsis

Question 30

what is specific damage by immune response?

Answer 30

minicry
cytokine induction
Toxins that inhibit immune function