Bacterial Pathogenesis (1/7)

Question 1

What genes are required to cause disease?

Answer 1

Attachment genes i.e. pili

Genes for all their metabolic requirements i.e. iron scavenging

Flagella for motility (note that it’s also immunostimulatory)

Toxins & their secretion – get secreted outside the cell

Question 2

What is a bundle forming pilus?

Answer 2

First step in attachment to epithelial cells i.e. to carbohydrate receptors

Question 3

What are siderophores? pyocyanin?

Answer 3

Siderophores = pigment that allows bacteria to scavenge iron

Pyocyanin = antioxidant/pigment that allows organism to deal with oxidative stress

Both are virulence factors

Question 4

What is the role of the flagella for a bacterium? In the innate immune system?

Answer 4

For bacterium: motility

For immune sys: it’s immunostimulatory: ligand for non-opsonic phagocytosis for macrophages via TLR activation & intracellularly can activate the inflammasome via caspase 1, IL-1 beta, IL-18

Question 5

What are the 2 major mechanisms by which bacteria can cause pathology?

Answer 5

1. Host inflammatory response that’s evoked by bacterial virulence factors
2. toxin release that can cause cessation of protein synthesis, nerve conduction, etc

Question 6

How does the inflammasome signal in response to flagella?

Answer 6

Cytoplasmic activation, caspase-1 activation, proinflammatory cell death; as this happens, immune cells get replenished

Question 7

What is the importance of LPS?

Answer 7

LPS = gram negative bacterial endotoxin

It activates TLR4 –> NF-kB –> chemokines –> recruite PMNs

Question 8

Why do some people get different severity of reactions when exposed to the same pathogen?

Answer 8

Polymorphisms

Example: TLR4 polymorphisms are implicated in susceptibility to septic shock

Question 9

What is a type III secretion system?

Answer 9

Enables pathogens to inject toxins into the cell

Pilum-mediated attachment, open the cell-cell junctions, actin/myosin contraction opens up, toxin goes through

ADP ribosylate enxyme targets Ras & messes with cytoskeleton

ExoU = phospholipase, destroys tissue

Type III toxins inject their own receptor!!

They stimulate an inflammatory response/diarrheal disease

Question 10

What is a quorum sensing system?

Answer 10

When you have a lot of bacteria in a group, they sense each other & upregulate the same genes, some of which can activate an immune response

Example= can make biofilms, which allow pathogens to colonize the airway