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Title: Populations of Escherichia coli in clinical samples of urinary tract infections and bacteraemia
Author: Alhashash, F. A.
ISNI:       0000 0004 5920 7962
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2015
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Extraintestinal pathogenic E. coli (ExPEC) strains are the main etiologic agent of urinary tract infections (UTIs). ExPEC strains are also reported to be the most common cause of bacteraemia in the world, which often originate from UTI. The population structure of UTI E. coli strains is well described in the literature with increased prevalence of multidrug resistance driven by extended spectrum β lactamases (ESBLs). ESBL carriage and multidrug resistance of bacteraemia E. coli is on the increase yet little information is available about their population structure. With the aim to define the bacteraemia population structure, E. coli isolated from urine samples and blood cultures were collected from the Nottingham University Hospital NHS trust over a five month period. Isolates were tested for antimicrobial resistance, ESBL and virulence associated gene (VAG) carriage, and were typed by MLST. Significantly higher ESBL driven multidrug resistant strains were observed in the bacteraemia E. coli compared to the UTI isolates with no significant difference in the carriage of VAGs. Our data shows a reduction in population diversity within the bacteraemia isolates compared to the concomitant urine sample population resulting in a small number of dominant sequence types (STs) (ST131, ST73, ST95) which is associated with ESBL conferred multi drug resistance and not specific virulence genes. This suggests that the increased prevalence of ESBL carriage in ExPEC isolates is leading to a selective advantage in a small number of dominant lineages causing bacteraemia in patients. Comparative genome analysis of selected isolates belonging to the dominant ST (ST73) from bacteraemia and UTI was performed to investigate the presence of bacteraemia specific loci that may explain the loss of diversity in bacteraemia. No genomic regions were identified specific for the bacteraemia ST73 isolates other than ESBL carriage. Plasmid profiling of the ESBL positive isolates of this ST73 group from bacteraemia and UTI identified diverse types of plasmids spread between the strains. No specific genomic loci were identified specific for ESBL positive ST73 isolates from bacteraemia and UTI. This concludes that random acquisition of ESBL plasmids by any ST73 E. coli may select for its progression to bacteraemia which is serious and debilitating. Our study provided a comprehensive snapshot of the E.coli population structure from contemporaneous clinical cases of UTI and bacteraemia. The large increase in multi-drug resistance in bacteraemia ExPEC populations compared to co-circulating UTI populations is of clinical concern and represents a challenge in control and treatment of serious extra-intestinal E. coli infections. This provides an important clinical insight into how common E. coli STs could adapt to become dominant bacteraemia agents.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available