A pilot study of the P. aeruginosa accessory genome in CF Infections

Up to 80% of adults with CF grow the bacterium Pseudomonas aeruginosa from their respiratory secretions at some point. Chronic colonization with this organism causes a more rapid decline in lung function and earlier death. As a result, substantial efforts have been devoted towards eradicating P. aeruginosa from the lungs of CF patients before chronic colonization is established. Unfortunately, these attempts frequently fail. We propose to use new genomic approaches and powerful animal models to identify P. aeruginosa factors that allow this bacterium to readily establish chronic colonization. A cornerstone of our approach is to take advantage of a valuable resource generated through support by the CFF: the EPIC trial. This study used collections of P. aeruginosa isolates that were either eradicated or persisted following antibiotic treatment of newly infected individuals with CF. We will compare the genomes of these two sets of isolates to identify genes associated with persistence. Likewise, we will compare the characteristics of these two sets of isolates in several animal models of infection to identify a laboratory system that adequately distinguishes eradicated from persistent isolates. These studies will lay the foundation for understanding how P. aeruginosa chronically colonizes the airways of CF patients, which will in turn identify bacterial factors that are candidate targets for novel agents that prevent chronic colonization. Such drugs may also have efficacy in treating chronically infected patients, who are currently refractory to eradication with antibiotics.