Grant: Operating Grant

Pseudomonas aeruginosa is a bacterium that causes severe, long-term (i.e. chronic) and often lethal infections in humans with chronic lung disease. The organism is innately resistant to many antibiotics and often develops what might be termed high-level antibiotic resistance during the infection, both of which compromise effective treatment of these lung infections. P. aeruginosa evolves in the chronically-infected lung, acquiring a series of mutations that allow it to adapt to this environment. Interestingly, there is increasing evidence that some of the adaptive mutations also promote resistance to antibiotics. Thus, long-term growth of P. aeruginosa in patients with chronic lung disease may predispose the organism to antibiotic resistance, making treatment of chronic P. aeruginosa lung infections difficult. The focus of this proposal is to identify the antibiotic resistance-promoting changes that occur in P. aeruginosa during chronic lung infections. The ultimate goal is to use this information in an effort to block or overcome resistance development in chronic lung infections caused by this organism.