The outcome after lung transplantation (LT) is worse than after other organ transplants. This is due to frequent allograft infections and development of chronic rejection (bronchiolitis obliterans syndrome; BOS). Pseudomonas aeruginosa is a particularly threatening bacterium responsible for severe post-transplant pneumonia and is associated with BOS. Almost all cystic fibrosis (CF) patients are colonized with P. aeruginosa before transplantation, and most of them have their allograft colonized by these same bacteria early after transplantation originating from their sinuses. Preventing allograft colonization by P. aeruginosa might reduce both infections and BOS, and therefore significantly impact post-LT survival. However, so far no medical intervention has been able to prevent this process. We hypothesize that composition and timing (dynamics) of colonization by the recipient host flora influences the establishment of pathogenic species. Potentially, the host flora might either be protective or a prerequisite for colonization/infection by pathogenic species.

Using sequential bronchoalveolar lavage samples obtained before and after transplantation from LT recipients of three Swiss transplant centers (Geneva, Lausanne and Zurich), we will recover P. aeruginosa and other bacterial species. Bacterial adaptation to the novel non-CF microenvironment will be tested by characterizing phenotypes important for colonization including motility, nutrient utilization, biofilm formation, hypermutators and quorum-sensing. We will further investigate the mechanisms involved in bacterial intra- and inter-species competition. The dynamics of total microbial communities during the allograft colonization will be studied using sequential metagenomic analysis.

We expect to gain insight into the adaptive responses of bacteria during colonization, as well as into the dynamic evolution of microbial communities, and to establish a possible correlation with clinical outcome. This should allow for better prediction of the risk of colonization by pathogenic species after LT. The results of intra- and inter-species competition mechanisms could identify targets for novel interventions, possibly preventing colonization by pathogenic bacteria. Altogether the results should improve the care of lung transplant recipients, increasing their comfort and life expectancy.