Antibody therapy against drug resistant Pseudomonas aeruginosa infections (11)

What are antibiotics?

Substances used to treat or prevent some types of bacterial infections

What are ESKAPE pathogens?

Clinically significant group of multi-drug resistant bacteria

What are those pathogens characterized by?

Their ability to evade antimicrobial activity through diverse resistance mechanisms

What does that mean for immunocompromised individuals?

That they are more sensitive to them because they cause opportunistic infections

What is the genus of the ESKAPE pathogens? (5)

1. Enterococcus

2. Staphylococcus

3. Klebsiella

4. Acinetobacter

5. Pseudomonas

6. Enterobacter

What are antibodies/immunoglobulins?

A large Y-shaped protein used by the immune system to identify and neutralize foreign objects (bacteria, viruses)

What do antibodies specifically recognize?

An antigen or a unique molecule of the pathogen

Variable region

Unique region that determines antigen specificity. Its antigen binding site is extremely specific.

Fc/effector region

Conserved region that is recognized by the immune system

What infection does Pseudomonas aeruginosa cause?

Pneumonia in ventilated patients

What type of pathogen is it?

A gram-negative opportunistic pathogen

What is the 1st virulence factor that Pseudomonas uses?

A Type 3 secretion system/injectisome

How does that injectisome work?

It allows bacterial escape form phagosomal killing by injecting multiple virulence factors into host cells (=pore)

What’s is the key element to the T3SS ?

PcrV subunit (or the tip of the needle)

What is the 2nd virulence factor in Pseudomonas?

Psl Exopolysaccaride (EPS)

How does EPS work?

It prevents the immune cells from recognizing the pathogen (+persistance)

What does the Anti-PcrV antibody allow?

Acidification of Pseudomonas

What does the Anti-Psl antibody allow?

To block the exopolysaccharide Psl function

How did both antibodies perform?

Phagocytosis increased significantly with Anti-Psl but Anti-PcrV mice cleared the infection better.

What was the response to those results?

The creation of MEDI3902 or an into body that combines anti-PcrV and anti-Psl.

What was the response to those results?

The creation of MEDI3902 or an into body that combines anti-PcrV and anti-Psl.

What was observed with MEDI3902?

Increased neutrophil acidification and localization to acidified compartments.