The phenotypic, genotypic and transcriptomic characterisation of a novel Pseudomonas aeruginosa small colony variant isolated from a chronic murine infection model

Irvine, Sharon C. (2017) The phenotypic, genotypic and transcriptomic characterisation of a novel Pseudomonas aeruginosa small colony variant isolated from a chronic murine infection model. PhD thesis, University of Glasgow.

Abstract

Phenotypic change is a hallmark of adaptation of Pseudomonas aeruginosa to the lung during chronic infection in patients with cystic fibrosis (CF). Well-characterised phenotypic variants include mucoid and small colony variants (SCVs), the appearance of which is associated with disease severity. In this thesis, P. aeruginosa SCVs isolated from the murine lung following the establishment of chronic infection are characterised at the phenotypic and genetic level. The isolated SCVs are shown to closely resemble those isolated from CF patients and conversion to the SCV phenotype is accompanied by transcriptional changes that include upregulation of key virulence determinants and the oxidative stress regulon, suggesting that selection of the SCVs in the lung is driven by the host immune response to chronic infection. Using a combination of single-molecule realtime (PacBio) and Illumina sequencing we identified the genetic switch for conversion to the SCV phenotype as a large genomic inversion through recombination between homologous regions of two rRNA operons. The observations that a highly similar inversion is observed in a recently sequenced P. aeruginosa SCV isolate from a patient with cystic fibrosis and that genomic inversion in S. aureus can also drive conversion to an SCV phenotype, suggests this may be a common mechanism through which diverse bacteria adapt to the environment of chronically inflamed host tissue.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: Walker, Dr. Daniel
• Date of Award: 2017
• Depositing User: Dr Sharon C Irvine
• Unique ID: glathesis:2017-8211
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 21 Jul 2017 13:40
• Last Modified: 19 Apr 2024 08:43
• Thesis DOI: 10.5525/gla.thesis.8211
• URI: https://theses.gla.ac.uk/id/eprint/8211