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Title: Pseudomonas aeruginosa pathogenesis in urinary tract infections
Author: Ebrahim, Hussain
ISNI:       0000 0004 9351 9011
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2019
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Urinary tract infections (UTIs) cause high morbidity, mortality and economic burden. Pseudomonas aeruginosa can cause persistent UTIs and it has many virulence factors including quorum sensing systems and iron acquisition mechanisms. Furthermore, this pathogen is highly resistant to antibiotics and has been highlighted by the World Health Organisation as a pathogen for which there is critical need for new antimicrobials. I have characterised P. aeruginosa UTI isolates from both the UK and Kuwait. The UTI isolates were variable in terms of their phenotypic characteristics and genomic composition. Multiple resistance genes linked to resistance to different classes of antibiotics including aminoglycosides, fluoroquinolones and β-lactams were identified from the sequence data using the CARD database, particularly in the isolates from Kuwait. These isolates were pan-resistance and multidrug resistance, with the ability to spread resistance via horizontal gene transfer. Laboratory media are commonly used to study bacteria in vitro. Nutrient rich media does not accurately reflect the physiological environment, prompting the development of multiple media mimicking human body fluids such as Artificial Urine Medium (AUM). My results show that bacterial responses in LB and AUM were highly different. AUM and urine showed similar responses with regards to the increase in proteins associated with iron acquisition mechanisms and of the decrease in proteins associated with the Type III secretion system. However, differences were observed in other important pathways such as those involved in phenazines production. This suggests that AUM is a more reflective media than LB to study P. aeruginosa UTI isolates, particularly when the environment needs to be highly controlled/consistent, such conditions cannot be controlled in urine. The difference in the protein abundance profile in AUM suggest that further optimisation of the medium could be performed for better resemblance of urine. Hormones are regulatory substances that are produced by the host and transported around the body. Sex-related hormones, oestrogen (oestradiol), progesterone and testosterone are examples of these. Previous studies have indicated that sex hormones such as oestradiol may modulate P. aeruginosa mucoidy and alter innate immune responses in females. In this study, treatment with all three hormones decreased the abundance of P. aeruginosa proteins associated with iron acquisition mechanisms. Furthermore, individual hormones also showed specific bacterial changes such as increased protein abundance in pqs quorum sensing mechanism by oestradiol compared to testosterone and progesterone. This study suggests that P. aeruginosa pathogenesis may be variable in UTI infections based on the host hormonal profile. Understanding the individual role of host factors could allow us to fully understand the contribution of host components and the impact these may have on infection susceptibility and outcome. Therefore, further research is required into the role of host components, in particular sex hormones, in host-pathogen interactions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral