A Metabolomics-Based Analysis of Acyl-Homoserine Lactone Quorum Sensing in Pseudomonas aeruginosa
type: CreativeWork
description: Pseudomonas aeruginosa is a metabolically versatile environmental bacterium that grows in extremely diverse habitats—from sea water to jet fuel—and is able to infect a large variety of organisms. It is a significant cause of human disease and is one of the most frequent healthcare-associated infections. P. aeruginosa uses a sophisticated gene regulatory network to adapt its growth strategy to these diverse environmental niches and the fluctuating conditions it encounters therein. The las and rhl “quorum sensing” (QS) intercellular communication systems play integral roles in this regulatory network and control the expression of factors important to the bacterium’s ecological fitness, including many secreted factors involved in nutrient acquisition, microbial competition, and virulence. These QS systems use diffusible acyl-homoserine lactone (AHL) signalling molecules to infer environmental parameters, including bacterial population density, and to coordinate behaviour across bacterial communities. This dissertation describes an investigation into the relationship between QS and small molecule primary metabolism, using metabolomic methods based on nuclear magnetic resonance spectroscopy and mass spectrometry. Analysis of extracellular metabolic profiles (the bacteria’s “metabolic footprint”) established that QS can modulate the uptake and excretion of primary metabolites and that this effect was strongest during the transition from exponential to stationary phase cell growth. Analysis of the cellular metabolome and proteome demonstrated that QS affected most major branches of primary metabolism, notably central carbon metabolism, amino acid metabolism and fatty acid metabolism. These data indicate that QS repressed acetogenesis and the oxidative C02-evolving portion of the TCA cycle, while inducing the glyoxylate bypass and arginine fermentation. QS also induced changes to fatty acid pools associated with lower membrane fluidity and higher chemical stability. Elevate…
abstract: Pseudomonas aeruginosa is a metabolically versatile environmental bacterium that grows in extremely diverse habitats—from sea water to jet fuel—and is able to infect a large variety of organisms. It is a significant cause of human disease and is one of the most frequent healthcare-associated infections. P. aeruginosa uses a sophisticated gene regulatory network to adapt its growth strategy to these diverse environmental niches and the fluctuating conditions it encounters therein. The las and rhl “quorum sensing” (QS) intercellular communication systems play integral roles in this regulatory network and control the expression of factors important to the bacterium’s ecological fitness, including many secreted factors involved in nutrient acquisition, microbial competition, and virulence. These QS systems use diffusible acyl-homoserine lactone (AHL) signalling molecules to infer environmental parameters, including bacterial population density, and to coordinate behaviour across bacterial communities. This dissertation describes an investigation into the relationship between QS and small molecule primary metabolism, using metabolomic methods based on nuclear magnetic resonance spectroscopy and mass spectrometry. Analysis of extracellular metabolic profiles (the bacteria’s “metabolic footprint”) established that QS can modulate the uptake and excretion of primary metabolites and that this effect was strongest during the transition from exponential to stationary phase cell growth. Analysis of the cellular metabolome and proteome demonstrated that QS affected most major branches of primary metabolism, notably central carbon metabolism, amino acid metabolism and fatty acid metabolism. These data indicate that QS repressed acetogenesis and the oxidative C02-evolving portion of the TCA cycle, while inducing the glyoxylate bypass and arginine fermentation. QS also induced changes to fatty acid pools associated with lower membrane fluidity and higher chemical stability. Elevate…
author: Davenport, Peter William
language: en
keywords: Pseudomonas aeruginosa, quorum sensing, metabolomics, intercellular signalling, bacterial physiology, functional genomics, mass spectrometry, nuclear magnetic resonance spectroscopy, bacterial metabolism
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/8f1b727a-1a75-4c14-a4d8-7b11e4363e22/download
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
date published: 2018-09-01
date modified: 2026-07-22T22:24:13Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.21807