Iron-Regulated Production of Antimicrobial Metabolites by Pseudomonas aeruginosa
AdvisorOglesby, Amanda G.
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AbstractCystic fibrosis (CF) is a hereditary disease characterized by the accumulation of thick, viscous mucus in the lungs. CF disease results in decreased pulmonary function and makes patients prone to chronic bacterial infections. The CF lung is a polymicrobial environment and includes many bacterial species. Early infection with Staphylococcus aureus is common, while Pseudomonas aeruginosa becomes the dominant pathogenic resident as disease progresses. This shift in microbial populations is still not well understood, but the ability of pathogens to obtain limiting nutrients, such as iron, may play a role. The work in this dissertation employed metabolomics, genetics, and biochemical approaches to show that P. aeruginosa alters its iron uptake mechanisms over the course of CF lung infection to adapt to the changing environment of the CF lung and to maintain iron homeostasis. Furthermore, I show that depletion of iron, an essential nutrient for P. aeruginosa growth and survival, enhances antimicrobial activity of this pathogen against S. aureus. I show that iron not only regulates the production of antimicrobial metabolites by P. aeruginosa, but also impacts the susceptibility of S. aureus to the effects of these metabolites. This work has expanded on the knowledge of how iron availability impacts polymicrobial interactions and the progression of CF lung disease.
DescriptionUniversity of Maryland, Baltimore. Pharmaceutical Sciences. Ph.D. 2016