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dc.contributor.advisorWhiteley, Marvin
dc.creatorHuse, Holly Kristenen
dc.date.accessioned2014-02-18T20:58:58Zen
dc.date.issued2013-12en
dc.date.submittedDecember 2013en
dc.identifier.urihttp://hdl.handle.net/2152/23236en
dc.descriptiontexten
dc.description.abstractChronic microbial infections result from persistent host colonization that is not cleared via the immune response or therapeutics. Within the host, microbes can undergo adaptive evolution, whereby beneficial traits promoting persistence arise due to selection; these traits can therefore affect disease outcomes and treatment strategies. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa is the primary cause of chronic, fatal respiratory infections in individuals with the heritable disease cystic fibrosis (CF). The goal of this dissertation is to identify adaptations that allow P. aeruginosa to persist in the host during chronic CF lung infection. To achieve this goal, P. aeruginosa was chronologically sampled from 3 CF patients, ranging from the first infecting bacterium (the ancestor) to ~40,000 generations post-infection. By comparing gene expression profiles of ancestral and evolved isolates sampled from multiple patients, I identified 24 parallel gene expression changes that occurred over time within each lineage, suggesting that these traits are beneficial to the bacterium. Because most of these traits had unknown physiological roles, I sought to characterize their biological significance. I used a gain-of-function genetic screen and discovered that a subset of these genes enhance biofilm formation, a sessile mode of growth proposed to be important during chronic CF lung infection. I showed that enhanced biofilm formation is due to increased production of the exopolysaccharide Psl, which is traditionally viewed as less critical for maintaining chronic infections than other virulence factors. Lastly, I demonstrated that a majority (~72%) of chronic P. aeruginosa isolates produce more Psl than their corresponding ancestor, suggesting that this exopolysaccharide is important during chronic infection and an adaptive trait.en
dc.format.mimetypeapplication/pdfen
dc.language.isoen_USen
dc.subjectPseudomonasen
dc.subjectEvolutionen
dc.subjectBiofilmen
dc.subjectPolysaccharideen
dc.subjectCystic fibrosisen
dc.subjectInfectionen
dc.titleAdaptation of Pseudomonas aeruginosa to the cystic fibrosis lung environmenten
dc.date.updated2014-02-18T20:58:58Zen
dc.description.departmentMicrobiologyen
thesis.degree.departmentMicrobiologyen
thesis.degree.disciplineMicrobiologyen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen


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