Jekyll and Hyde: The switch from environmental resident to antibiotic-resistant superbug in Pseudomonas aeruginosa

Naik, Dixita Komal (2023) Jekyll and Hyde: The switch from environmental resident to antibiotic-resistant superbug in Pseudomonas aeruginosa. Doctoral thesis, University of East Anglia.

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Abstract

Pseudomonas aeruginosa strains embrace numerous strategies to enable their survival across a diverse range of environments. Historically, analysis of the core genome phylogeny has displayed five major clades one of which appeared distant from the other groups. This thesis presents detailed analysis of the divergent clade, characterised by the P. aeruginosa PA7 strain, to confirm the 16S rRNA sequence is identical to other P. aeruginosa strains and is unlike those belonging to other Pseudomonas spp. In contrast, methods utilising the whole genome reveals that this divergent group of PA7-like strains is distinctive enough to form its own separate species. Furthermore, detailed analysis of the P. aeruginosa core genome revealed groups of strains linked to either clinical or environmental origins. Niche associated core groups could be characterised by both gene presence and absence, as well as by single nucleotide polymorphisms. In terms of the clustering based on the P. aeruginosa accessory genome, few accessory clusters were spread across multiple core groups. This, coupled with a lack of gene flow between the core groups, suggests that the core genome provides a basis for niche adaption that is completed by the characteristics of the accessory genome. Additionally, this thesis sought to investigate how environmental P. aeruginosa isolates adapt to clinical niches by using the presence of chloramphenicol and ciprofloxacin antibiotics to simulate a clinical niche. This uncovered the trajectories taken by the organism to resist antibiotic pressure which involved “switching-on” intrinsically encoded efflux pumps. After the removal of antibiotic pressure, the efflux systems were “switched-off” by additional mutations. Whilst these mutations reduce antibiotic tolerance, they also alter fitness to varying degrees relative to the ancestral parent and mutant strains.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Nicola Veasy
Date Deposited: 27 Mar 2024 12:05
Last Modified: 27 Mar 2024 12:05
URI: https://ueaeprints.uea.ac.uk/id/eprint/94788
DOI:

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