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Title: Molecular epidemiology of uropathogenic Escherichia coli in North West England and characterisation of the ST131 clone in the region
Author: Gibreel, Tarek Mohamed
ISNI:       0000 0004 2709 2101
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2011
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Multilocus Sequence-Typing (MLST) is a phylogenetic technique based on the detection of differences in multiple conserved housekeeping genes. Together with powerful evaluation software, MLST provides an extensive classification scheme for highly diverse species. However, despite the increasing use of MLST as a trusted epidemiological tool, the population structure of UPEC has been poorly studied using this technique, as most of the previous studies conducted have been limited either by bias towards certain characteristics, such as antimicrobial resistance and serogroup, or included a limited number of strains. Such studies can give a false impression of the population structure due to overrepresentation of certain Sequence types (STs).In this thesis, MLST was applied to 300 E. coli isolates collected from in the North West of England between June 2007 and June 2009. Firstly, the prevalence, diversity, epidemiological relationships and phylogenetic origins of the identified STs were determined. Secondly, possible associations of key UPEC STs with other genotypic and phenotypic profiles were assessed. Thirdly, as ST131 was recently reported as one of the most successful UPEC clones, an extensive examination of isolates of this clone was carried out involving identification of multiple drug resistant subclones and attempts were made to recognise putative predictor markers for identification of the ST131 clone.MLST analysis of the studied population revealed a consistent profile of STs that occurred repeatedly in the collection. It consisted primarily of ST73 (16%) followed by ST131 (13.3%), ST69 (9%), ST95 (6.3%), ST10 (4.3%), ST127 (3.6%), ST14 (2.6%) and ST405 (1.6%) some of the STs (ST127 and ST80) in the panel have never been reported as remarkable uropathogens.The broad range of virulence factor (VF) genes screened here allowed the recognition of VF patterns significantly associated with different STs. Most notably, ST127, which, based on phylogenetic analysis, appears to be a newly evolved clone, gave the highest virulence score. This virulent genotype may permit survival of ST127 isolates in the population long enough for them to gain antibiotic resistance. In contrast, multidrug resistant isolates of the ST131 clone were defined by a low virulence score and distinctive VF profiles.Metabolic reactions have been conventionally used for the classification of bacteria into families and species. Interestingly, in the assessment of the metabolic activity of different STs, members of the ST131 clone showed a high metabolic capacity compared to those of other STs, which may compensate for the low virulence capacity and explain the virulence reported for members of this ST. In contrast, ST127 showed the lowest metabolic capacity, even though it held the highest VF-score among the commonly detected STs. Multivariate logistic regression analysis demonstrated that ST131 is best described by its fluoroquinolone resistance and possession of PAI, the ibeA gene and expression of DR antigen-specific adhesins, whereas the O25b-CTX-M-15 ST131 sub-clone was only differentiated from the rest of the ST131 clone members by the production of Extended spectrum Beta-lactamase (ESBL) enzymes.
Supervisor: Dodgson, Andrew ; Upton, Mathew Sponsor: Libyan government
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Molecular ; icemiology ; Uropathogenic E. coli ; ST131