Mechanisms of DNA repair and damage tolerance in Pseudomonas aeruginosa: Implications for cystic fibrosis patients
Sanders, Laurie Heather
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P. aeruginosa is a human opportunistic pathogen that chronically infects the lungs of cystic fibrosis patients and is the leading cause of morbidity and mortality of people afflicted with this disease. A striking correlation between mutagenesis and persistence of P. aeruginosa has been reported. Initial colonization of the CF airway by P. aeruginosa results in intermittent infection. However, the subsequent rapid adaptation of the initially colonized P. aeruginosa to the CF airways results in chronic infection that lasts from years to decades, and is never fully eradicated. Importantly, P. aeruginosa continues to acquire adaptive changes throughout the course of the infection that further contribute to the persistence of the infection. One centrally important yet unanswered question in the field pertains to the molecular mechanism(s) by which P. aeruginosa acquires these mutations enabling it to adapt and persist to the harsh environment of the CF airways. The goal of my thesis was to gain insights into the fundamental mechanisms underlying mutagenesis that may contribute to P. aeruginosa pathogenesis. Specifically, my efforts in this area over the last several years have resulted in a working model to describe the relationship between DNA repair, mutagenesis, and adaptation of P. aeruginosa to CF airways.