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Cystic fibrosis: regulation of chronic infections

Understanding the role of a bacterial toxin in pulmonary infections in cystic fibrosis patients

The Air Liquide Foundation supports the Institut Pasteur in Paris in the fight against bacterial infections of the lungs. This project aims to understand how the ExoY toxin produced by the bacterium Pseudomonas aeruginosa affects the lung cells of cystic fibrosis patients. This toxin seems to enable the bacteria to settle and persist in the lungs. By studying its mode of action, we hope to find new ways to better treat these chronic lung infections.

© L. Touqui - Dr Touqui's team

A bacterium with a strong adaptive capacity

The Pseudomonas aeruginosa bacterium has a strong adaptability to a large number of hostile environments. It can also quickly develop a resistance to antibiotics following chronic infections and become very virulent. This leads to a therapeutic impasse and represents a global health threat today.

The Pseudomonas aeruginosa bacterium is classified by the World Health Organization in the critical priority list of multi-resistant bacteria.

Controlling lung infection

The goal of Dr. Touqui and his team at the Institut Pasteur is to find an interesting therapeutic target for the control of pulmonary infection by Pseudomonas aeruginosa, one of the major causes of mortality in patients with cystic fibrosis. The virulence of this bacterium is enhanced by its ability to inject exotoxins directly into the host cell. A better understanding of the role and mode of action of exotoxins would allow a better understanding of how this bacterium settles in a long-term and irreversible manner in the airways of cystic fibrosis patients, but also of immunocompromised patients infected by the bacterium.

ExoY, a key to understanding Pseudomonas aeruginosa

The aim of this research project is to study in particular the exotoxin ExoY, one of the four exotoxins produced by Pseudomonas aeruginosa. Preliminary studies suggest that the exotoxin ExoY stimulates the cellular defense process - phagocytosis - of this bacteria. It may even have an inhibitory effect in inducing the process of self-destruction (apoptosis) of the cells that the bacteria attacks. The study of this exotoxin remains to be developed. Therefore this project aims to analyse the role of ExoY in:

  • the regulation of the phagocytosis of Pseudomonas aeruginosa by white blood cells (macrophages) 
  • the inflammatory response of human respiratory epithelial cells and macrophages 
  • Pseudomonas aeruginosa-induced self-destruction (apoptosis) of human respiratory cells

I am very proud to be able to contribute my expertise as a biological researcher to the development of a fruitful collaboration between the Air Liquide Foundation and the Institut Pasteur. Supporting the ExoY project allows us to be involved from the earliest stages of basic research, key steps in the development of innovative medicines for cystic fibrosis patients.

Aude MILET, PhD

Scientific Affairs Manager - Head of Medical Exploratory Team, Partnership and Strategy - WBL MSI

How the Air Liquide Foundation is participating

The Air Liquide Foundation is contributing to the acquisition of the consumables necessary for the research project and the operating costs from 2021 to 2024. The project is monitored by an Air Liquide Medical Systems Expert.

Institut Pasteur