Bacterial chassis for treating ventilator-associated pneumonia (vap)
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.