Pseudomonas aeruginosa pathogenesis during cystic fibrosis lung infection and metabolism of lung surfactant component phosphatidylcholine
Date
2008
Authors
Contributor
Advisor
Department
Instructor
Depositor
Speaker
Researcher
Consultant
Interviewer
Narrator
Transcriber
Annotator
Journal Title
Journal ISSN
Volume Title
Publisher
University of Hawaii at Manoa
Volume
Number/Issue
Starting Page
Ending Page
Alternative Title
Abstract
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.
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.
Description
Keywords
Citation
Extent
Format
Geographic Location
Time Period
Related To
Theses for the degree of Doctor of Philosophy (University of Hawaii at Manoa). Microbiology; no. 5125
Related To (URI)
Table of Contents
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.
Rights Holder
Local Contexts
Collections
Email libraryada-l@lists.hawaii.edu if you need this content in ADA-compliant format.