Descripción del proyecto
Enfrentar a las bacterias las unas contra las otras: Un nuevo enfoque para tratar la neumonía asociada al respirador
La neumonía asociada al respirador (NAR, o VAP por sus siglas en inglés) es causada por las biopelículas de «Pseudomonas aeruginosa» y «Staphylococcus aureus» en los tubos endotraqueales y se produce en el 9-27 % de todos los pacientes intubados. La NAR provoca inflamación crónica y constituye la principal causa de mortalidad de pacientes hospitalizados. El proyecto MycoVAP, financiado con fondos europeos, se propone diseñar bacterias para administrar agentes terapéuticos de forma local y disolver las biopelículas de «P. aeruginosa» y «S. aureus» para tratar la NAR. Para ello, los científicos utilizarán «Mycoplasma pneumoniae», un patógeno leve del pulmón humano, como vector de administración de antibióticos y evaluarán su eficacia en modelos murinos de formación de biopelículas.
Objetivo
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.
Ámbito científico
- 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
Programa(s)
Régimen de financiación
ERC-POC - Proof of Concept GrantInstitución de acogida
08003 Barcelona
España