Description du projet
Monter les bactéries les unes contre les autres: une nouvelle approche pour traiter la pneumonie associée au ventilateur
La pneumonie associée au ventilateur (PAV) est causée par des biofilms de Pseudomonas aeruginosa et/ou de Staphylococcus aureus sur des tubes endotrachéaux et survient chez 9 à 27 % de tous les patients intubés. La PAV entraîne l’inflammation chronique et constitue la première cause de mortalité des patients hospitalisés. Le projet MycoVAP, financé par l’UE, propose de concevoir des bactéries pour administrer des agents thérapeutiques localement et dissoudre les biofilms S. aureus et P. aeruginosa comme traitement de la PAV. À cette fin, les chercheurs utiliseront le pathogène pulmonaire humain bénin Mycoplasma pneumoniae comme véhicule d’administration d’antibiotiques et évalueront son efficacité dans des modèles murins de formation de biofilm.
Objectif
Among 65-80% of human infections are associated to biofilms, especially in respiratory infections or those associated with catheters. Endotracheal tube (ETT) biofilm is related to the development of ventilator-associated pneumonia (VAP), which occurs in 9–27% of all intubated patients. Those ETT-biofilms are mainly formed by Pseudomonas aeruginosa and/or Staphylococcus aureus, forming a protective barrier against antibiotics and the host immune system. The consequence of VAP is chronic inflammation resulting in slow but continuous decrease of lung function, which is the primary cause of mortality of patients at hospital wards, and is also associated with increased hospital morbidity; duration of hospitalization and consequently health care costs.
Engineering bacteria to deliver locally therapeutic agents or to present antigens for vaccination is an emerging area of research with great clinical potential. Up to date, an attenuated BCG strain, used for prostate cancer vaccination, is the only example of a living bacteria used for human therapy. However, there are several studies worldwide at preclinical stage addressing the use of engineered bacteria for human therapy.
We suggest here to test a non-pathogenic chassis of the mild human lung pathogen Mycoplasma pneumoniae, engineered to dissolve biofilms of S. aureus and P. aeruginosa for the treatment of VAP. The specific objectives of this proposal are: First, to confirm the safety of our bacterial chassis in the lung of animal models (mice and pigs). Second, to test the capacity of our engineered chassis to eliminate bacterial biofilms formed in endotracheal tubes and in mice models of biofilm formation. Success in both objectives will open the way to test our chassis in pig models of VAP as a first step towards its application in humans.
Champ scientifique
- medical and health sciencesclinical medicineoncologyprostate cancer
- medical and health sciencesclinical medicinepneumology
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
Programme(s)
Régime de financement
ERC-POC - Proof of Concept GrantInstitution d’accueil
08003 Barcelona
Espagne