Toxins II

What does the cholera toxin stimulate? What does this lead to?

Adenylyl cyclase activity leading to increase of host cytoplasmic cAMP levels. This can lead to massive disruption of cell function and fluid release

What are the symptoms of cholera toxin?

Copious diarrhea that is observed as rice water stool (liters) and rapid dehydration and organ dysfunction

What is a toxin co-regulated pilus? Does vibrio cholerae have one?

It is where binding to host cells and toxin expression is coordinated by a single transcription factor. Yes

Does cholera have a high or low infectious dose? How can you get it?

High but humans get it through water consumption and bacteria forming biofilms on algae

Does cholera do well in the acidity of the stomach?

No

What type of toxin is the cholera toxin?

AB5 toxin

What is the cholera toxin associated with?

A phage element that integrated in the chromosome of bacteria (associated with a bacterial phage that has inserted the genes from the toxin into the bacteria that has uptake it so the toxin genes are acquired through transduction)

Describe what happens in the vibrio cholerae pathway

1. Vibrio cholerae produces cholera toxin

2. Cholera toxin will bind to a receptor on a host cell

3. This increases adenylate cyclase activity leading to increase of cAMP

4. cAMP stimulates the release of sodium, potassium, chlorine, and bicarbonate ions

5. Water is also expelled resulting in diarrhea and ion imbalance

Does staphylococcus aureus have various morbidities? If yes, what are they?

Yes and they are skin infections, sepsis, respiratory infections, and even diabetic foot ulcers

Can staphylococcus aureus be detrimental if it gets into places where it shouldn’t be?

Yes

What is sepsis?

It is a blood borne infection and can get into a variety of organs and tissues making it challenging to treat

What does staphylococcus aureus have the power to do? Is this a hallmark feature of this pathogen?

It can modulate the immune system of the host it is infecting and is altering or reprogramming to its advantage (is an immunomodulatory pathogen). Yes

What does staphylococcus aureus secrete?

Various toxins and virulence factors. Also exotoxins (toxins at a distance) and super antigens (SAg)

What is an example of a virulence factor that staphylococcus aureus secretes? What does it do?

Sortases which are involved in anchoring

What does super antigen mean?

It is good at stimulating the immune system and at being antigenic

What is a disease associated with staphylococcus aureus?

Toxic shock syndrome and super absorbant tampons are a major risk factor associated with this disease

How can staphylococcus aureus cause toxic shock syndrome?

Staphylococcus aureus can get stuck in your vagina when inserting a tampon and get into your bloodstream through tiny cuts. Staphylococcus aureus will produce bacterial SAg which will be processed and presented on MHC II to TCRs. This drives extensive T cell activation and cytokine release resulting in a cytokine storm

What does a cytokine storm lead to if you can’t dial it back?

Septic shock

What are other organ specific pathologies associated with SAg?

Endocarditis, pneumonia, and bacteria (sepsis)

What do super antigens promote?

Staphylococcus aureus bloodstream infection by eliciting pathogenic interferon-gamma production

What does IFN-y elicit?

A protective immune response by activating macrophages and inducing nitric oxide production

What happens if there is too much IFN-y (dysregulation)?

It results in excessive inflammation leading to signalling hyper activation. There is an exaggerated immune response to physiological stimuli which eventually leads to tissue damage

How is the pathogen producing an exaggerated immune response?

By dysregulation through production of too much IFN-y

What is the pathology being driven by?

1. The dysregulated host response

2. Bacteria

How would you treat a patient with too much IFN-y? What happens if antibiotics are delivered too late?

Give them something anti-inflammatory. They can’t save you because there is now too much tissue damage due to excessive immune response