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Title: Understanding within patient diversity of Uropathogenic Escherichia coli
Author: Bedaiwi, Ruqaiah I.
ISNI:       0000 0004 7430 412X
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2018
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Urinary tract infections (UTIs) are one of the most common human infections worldwide. UTI is caused by a wide range of Gram-positive and Gram-negative pathogens with Uropathogenic E. coli (UPEC) the most common causative pathogen. In clinical microbiology, diagnosis, analysis and treatment are based on single colony selection of a homogenous bacterial population. However, recent work on infections such as cystic fibrosis has highlighted the presence of multiple phenotypic and genotypic variants within a single infected patient. A study comparing bacteria isolated from urine and blood samples from patients with urosepsis showed the presence of multiple sequence types of E. coli within a single patient. Therefore, here we present work investigating the level of within-patient diversity of UPEC at a phenotypic and genotypic level. Forty-two urine samples were collected and antibiotic sensitivity testing performed on each well-isolated colony. Samples are classified based on their sensitivity profiles into three patterns: identical resistance profile, low diversity resistance profiles and highly diverse resistance profiles. Nine urine samples were categorized as having highly diverse resistance profiles. Phenotypic assays of bacteria from the highly diverse group show variation in motility, biofilm formation and association and invasion assays. To determine the phenotypic baseline diversity level, the highly diverse resistance profile samples were compared with samples that were shown to have a homogenous population, and eight randomly selected samples with low diversity patterns. Bacteria from both patterns show no phenotypic variation. We further analysed the levels of genotypic diversity between sample isolates. We compared bacteria from highly diverse resistance profiles using whole-genome sequence data in order to correlate the phenotypic diversity with genetic changes. Together our data is the most high-resolution snapshot to date-of the levels of extant diversity of UPEC within patients with UTI.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available