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Title: Pseudomonas aeruginosa pathogenesis during cystic fibrosis lung infection and metabolism of lung surfactant component phosphatidylcholine 
Author: Son, Mike Seong
Date: 2008
Description: Includes supplementary digital materials. Thesis (Ph.D.)--University of Hawaii at Manoa, 2008. Pseudomonas aeruginosa, an opportunistic Gram-negative bacterium, is the principal cause of hospital-acquired pneumonia, and is responsible for the high morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa also causes a wide range of human diseases including otitis media, keratitis, endocarditis, osteochondritis, pyelonephritis, cellulites and septicemia. Despite the considerable effort expended toward studying P. aeruginosa infections and virulence expression, the pathogenesis of P. aeruginosa-associated diseases and the ability of P. aeruginosa to reach high cell density (HCD) during chronic lung infections in CF patients remains enigmatic. We hypothesized that in the lung environment, P. aeruginosa degrades the naturally occurring lung surfactant component phosphatidylcholine (PC), as a nutrient source to afford HCD replication and maintenance. To test this central hypothesis, I have conducted microarray and real-time RT-PCR experiments directly on sputum samples from two chronically infected CF patients to obtain a snap shot of the metabolic profile of P. aeruginosa populations. The microarray and real-time RT-PCR data provide strong evidence substantiating our initial hypothesis that PC may serve as a nutrient source to afford HCD replication and maintenance. Using bioinformatics and the microarray data, I was able to identify the PC degradative genes expressed during P. aeruginosa lung infection, including the fatty acid degradative (fad), choline metabolism (bet), and glycerol metabolism (glp) genes. The bet and glp pathways have been previously characterized, however, the fad pathway remains a mystery and can only be predicted based on the established E. coli fad pathway. Using this pathway as a model, I initiated investigations into deciphering this pathway in P. aeruginosa. I present here the characterization of the fadD genes (acyl-CoA synthetases), preliminary data on the characterization of the fadBA operons (acyl-CoA thiolases and acyl-CoA dehydrogenases), and data that link the association of the fad, bet, and glp pathways in regard to PC and PC component degradation. Includes bibliographical references (leaves xxx-xxx). Also available by subscription via World Wide Web 293 leaves, bound 29 cm
ISBN: 9780549812647
URI: http://hdl.handle.net/10125/20718
Rights: All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.

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